Dr Frassetto: Unique Opportunity to Drive Paleo Diet Study v. ADA Whole Wheat/Gluten 'Healthy Diet' for PCOS

Crowd-Sourced n=4

Thank you all Gentle Readers for participating earlier in one of the first gut microbiome QS study when I posted on Crowd-Sourced N=4: A Family Science Project of Resistant Starch on Gut Biome

Allan and his family reported their self monitored blood glucoses here. AmGut results soon as it takes about half a year.




UCSF Paleo Diet v ADA Whole Wheat Healthy Diet for PCOS

At UCSF Dr Lynda Frassetto et al are requesting help to prove the value and merit of the paleo diet for insulin resistant states such as PCOS. She is working collaboratively with other researchers to obtain funding for the next landmark study. What they collect via Crowdfund can be retained even if they do not reach the $40,000 goal. Dr Frassetto and I believe the paleo diet offers many hormonal and cognitive/behavioral benefits for those with insulin resistant states. I've spoken with Dr Frassetto to promote the diet at an EBT conference for emotional behavior therapy (Wired for Joy) because their participants see great mental and brain changes that complement the program.

What is needed is well designed and articulated studies like her earlier, seminal Paleo study that showed dramatic normalization of blood pressures in pre-hypertensive adults. This was not a low carb study but a basic, no grains, no legumes, no dairy paleo diet including some tubers (carrots, yams, etc). Her goal is to prove health benefits again for a group of patients that have few medical options (metformin, starvation weight loss diets, IVF, fertility treatment, etc). As you are aware in the paleosphere, many cases of spontaneous fertility and resolution of PCOS are commonplace.

A few days ago, they opened their UCSF-Crowdfund account and received $2855 already. Government funding has become scarcer of late. Many of the medical personnel for this study are in fact all volunteering their time according to Dr Frassetto. Unlike the prior study, outpatient food is not provided. Nutri Sci students (like I used to be LOL) from UC Berkeley will be volunteering to counsel diet information to trial participants. Costs for Free-testosterone, insulin, and other lab hormone measurements will be covered by funds collected.

Polycystic ovary syndrome (PCOS) is a syndrome which includes elevated androgen levels, irregular menstrual cycles and insulin resistance. Standard treatments, which include weight loss and medications to improve insulin secretion are only partly successful, and may require that young women take medications for decades.
The study investigators have been evaluating the effects of specific diets on insulin resistance in healthy volunteers and subjects with type 2 diabetes, and have found that subjects with insulin resistance seem to respond particularly well to these diet regimens.
Volunteers with PCOS are being asked to participate to see if following these diets can help regularize your menstrual cycles. The results of this study may help improve fertility treatments for women with PCOS.

An incentive from UCSF has thrown in:

Special early-bird incentive: Meet us at the Ancestral Health Symposium

Dr. Lynda Frassetto and Dr. Ashley Mason will be attending the Ancestral Health Symposium in Berkeley, CA August 7-9. We'd be happy to meet with you and talk about the study -- or if you donate at the $250 level, we'll take you to lunch and talk about anything you want!

Project Details ~~  http://clinicaltrials.gov/ct2/show/NCT02190097

How we'll spend the money

All $40,000 will go to costs for the study – the study personnel are all volunteering their time! Here's our approximate budget:

$20,000: Laboratory tests of insulin resistance and other biological outcomes.
$12,000: Research supplies and lab space.
$4000: Payments to participants for providing questionnaires, urine and blood samples, and uterine images.
$4000: Tracking and staying in touch with participants, data entry and administrative support.

Stephan G. at Whole Health also shares his thoughts: HERE

Thank you for your support!

Two Case Studies -- Diarrhea-IBS and Constipation-IBS and GI Fx Stool Test: Overgrowth of Pathobiont Klebsiella, Fungi Rhodotorula and super-low commensal Clostridia

Here is a functional medicine case -- 5 year old austic boy with constipation-IBS (credit: GDX Diagnostics)

Klebsiella oxytoca + Fungal Rhodotorula
Small Intestine Overgrowth
Credit: GDX Diagnostics

Buttloads of Butyrate flooding the whole body
Due to SIBO/SIFO

Per GDX/Metametrix:

• Here we find an even more severe overgrowth of K. oxytoca. Note that the assay is able to keep on  counting target genomes over many orders of magnitude. Here the oxytoca is present at 1.48 x 109 /gm, and  this child also shows concurrent extremely high levels of Rhodotorula sp. Incidence of Rhodotorula in our results is higher that from culture techniques, probably because it is identified microscopically, but grows poorly in usual culture media. 
• Plenty of metabolic activity is shown by the abundant SCFA and balanced percentages. Note the normal level of Lactoferrin, showing lack of inflammatory involvement currently in this patient with very active IBS due to profound microbial overgrowth. The immune barrier is weakened as shown by low sIgA. 
• Antibacterials and antifungals according to sensitivities. Immune support with glutamine (consider colostrums) and glutathione. Investigate food intolerances to lower the loading of GALT 

My assessment from the data on the GI FX stool test:

1. Overgrowth of pathobiont Klebsiella oxytoca (likely including small intestinal location)
2. Fungal overgrowth of Rhodotorula
3. Low commensal Clostridia (should be MUCH MUCH higher)
4. Low fecal sIgA (immunocompromised)
5. SUPER HIGH BUTYRATE and other SCFAs (because a SUPER BOWL FERMENTATION PARTY is going on in the small intestines and possibly colon due to inappropriate bacterial overgrowths)
6. Poor mood, poor sleep, possible anxiety secondary to dysbiosis-related failure of tryptophan to be synthesized to serotonin and serotonin to melatonin. 80-95% of serotonin are produced in the gut.  Dysbiosis affects gut conversion of tyrosine to dopamine.

C-IBS needs tons of weeding weeding weeding......................................

And replenishment and repopulation of SBO commensals/fermented foods, basically the 7-Steps to cure intestinal permeability and SIBO/SIFO, small intestine bacterial and fungal overgrowth.

How does this occur? After a round of gastroenteritis or antibiotics, the commensal organisms and fungi that safeguard our gut domain are reduced in number. The pathogenic strains emerge without these.  Soon yeasts, fungi and aggressive bacterial take root in places that are normally kept clear. The small intestines are a frail target -- only one cell layer thick.  Full of moisture, oxygen, intermittently constant food, and a rich blood supply.  Once fungi or bacterial take hold, food can no longer be digested well.  The GI barrier becomes broken down.

For the host, bloating or brain fog are frequent symptoms.


Here are my thoughts on the spectrum of hyper-permeability/leaky gut/SIBO/SIFO symptoms:

(a) Mildly Intolerant (gas, bloating, constipation, diarrhea, heartburn, ulcers, mental fog, cavities, enamel defects, nutritional deficiencies, anemia, vitamin B12 deficiency, hair loss, low thyroid, food cravings)

(b) Moderate (depression, anxious, allergies, ADHD, autism/spectrum, cardiovascular disease, Type 2 diabetes, osteoporosis, bone fractures, PCOS, fibroids, miscarriages, nerve pain, seizures, joint arthritis)

(c) Severe (failure to thrive, weight loss, weight gain, rashes, mood swings, infertility, migraines, bloody stools, bipolar, psychiatric disorders, alcoholism, cancer, autoimmune diseases, T1DM, celiac, rheumatoid arthritis).



In autism and other spectrum conditions, the gut-brain axis is broken.  In many cases, autism is reversed once the gut is fixed and no longer spilling out undigested food particles (gluten, casein) which resemble body proteins and other proteins of microbial origins.  In this case, like many spectrum cases, both bacterial and fungal overgrowths are present and the absent of commensals such as Clostridia. The problem in this C-IBS (constipation dominant IBS) case is not insufficient butyrate, but actually food fermenting excessively in the small intestines by 'regular/good' bacteria in the inappropriate place. Once a commensal grows aggressively, it can switch to a pathobiont status, exploring and invading an ecological niche.

One of the benefits of the 7-Steps to cure SIBO/SIFO that it is aligned to our ancestral heritage and tight association with the soil and abundant earth.  The earth not only feeds us with crops and herds but is the 'horticulture' that also provide wonderful organisms that serve to maintain the 'lawn of our gut' by weeding, weeding and weeding [hat tip: Brent Pottenger and here is his stellar gut GDX GI FX testing].


The benefits of SBOs (soil based organisms) are:
--they are the key apex predators that control the growth of smaller critters and predators in the gut ecosystem
--weed out and decrease populations of pathogens
--secrete antifungals
--secrete antimicrobials
--tighten up loose intestinal junctions in hyper-permeability
--eat fiber (soluble, insolube fiber and resistant starches)
--provide food and gases for bottom feeders
--ferment fiber into butyrate which is an antimicrobial
--make butyrate which is a potent agonist for GPR41 receptors which immunomodulate and control inflammation
--improve immunity which improve food intolerances, asthma/allergies and (for me) gluten and dairy allergies
--associated with reversed autoimmune diseases (prior animal pharm)




Case Study (Credit: FTA):

Alex W. // Jan 21, 2014 at 17:51

I’d like to add a success story here. Last August, just a week after starting graduate school, I came down with an intense bout of IBS-D (to keep it clean). Not unusual, as I’ve had the flu before. But this ‘flu’ did not stop, and stranger things began to happen. I developed tinnitus, neuropathy, dizziness, fatigue, muscle twitches and my sleep was terrible. 6 weeks later, I had lost 25 pounds (that I didn’t need to lose) and I was barely able to get out of bed. A colonoscopy, endoscopy, stool examination, countless blood tests and specialists later and still no answers. I took a medical leave from my program, and had to return to my home in California because I was no longer able to take care of myself.
It was around this time that I began experimenting with SCD and GAPS style diets. They did prove to help with some symptoms, but not all, and not with much speed. In fact, I would say that I got worse on these diets, as my sleep became a struggle, and that set everything back. Supplements like Vitamin C, Colostrum and DGL helped but were definitely not the answer, either. It was late December, and I had to make the call whether or not I was going back to school. I decided to go back out of desperation for wanting to be better, without really having made any progress. Not a wise decision, but I got lucky.
It was just two weeks ago, just at the start of the semester, that I began to follow the advice of Dr. BG over at Animal Pharm blog on correcting SIBO, as well as the advice here about resistant starch. I am so, so glad to say that I am 90% back to normal. My tinnitus is almost gone, my muscle twitching is nearly gone, my sleep is incredibly better. I can finally go back to teaching and researching without fears of passing out in the middle of class. The two biggest factors in my success was the inclusion of properly prepared starches (in Perfect Health Diet amounts) and supplementing with potato starch and psyllium husk twice a day.
I can’t speak for all the other successes and failures when it comes to variable carb intakes, potato starch supplementation and general paleo-style eating, but it worked for me. So thank you Tim, Rich, Grace and everyone else who’s been posting about this stuff. I’m not shitting you (har har) when I say that you saved my young life.

Have you had success with the 7-Steps?
What are the challenges?
Are you seeing improvements and optimization of gut/brain/muscle/genitalia??

I can't wait to hear your stories...

Two C elegans Articles and Two Success Cases With The 7-Steps To Cure SIBO

Appears Just Like Human Dysbiosis/SIFO/SIBO
Worms need microbes too: microbiota, health
and aging in Caenorhabditis elegans
Cabreiro, Gems, 2013

Worms need microbes too: microbiota, health and aging in Caenorhabditis elegans.
Cabreiro F, Gems D.
EMBO Mol Med. 2013 Sep;5(9):1300-10.


Worms as Human Aging Models and Worm SIFO/SIBO

Humans are one of the highest form of eukaryotes and worms, the simplest, most elegant.  C. elegans nematodes have nearly the full suite of homolog nuclear receptors, IGF, insulin, and  AMPK pathways. They have a gut microbiota as well and mutualistic health of the microbiota mirrors their longevity.  Careiro and Gems discuss in the above article how bacterial proliferation of the nematode gut highly correlates with reduced immunity and aging.  While the relationship is mutualistic, both microbes and host benefit.  The microbes have a happy home, warmth and food.  For the worm host, the gains are immeasurable -- happy immunity, vitamins/minerals and longevity. One of the best growth media for C elegans is B subtilis, the soil based organism I talk a lot about. When growth media are switched out to bacteria which are less mutualistic (like pure E. coli), the nematodes have a very short life. Blockages of the lumen occur; worm constipation and something analogous to mammalian SIFO/SIBO.  When the media has a natural SBO like B subtilis, the nematodes thrive, have no signs of aging or bacterial proliferation and demonstrate notable worm longevity.  Any intervention in fact that prevents bacterial proliferation (SIFO/SIBO) extends lifespans they reveal.  Makes sense, no?

Two of my favorite probiotics contain B subtilis (Prescript Assist and AMD Syntol). Foods that contain B subtilis include any ancestrally prepared and fermented foods that include both protein and starch: gochujang, natto, fermented black bean sauce, Thai shrimp sauces, etc.

Prior Animal Pharm:

• Cure SIBO Step #1 Eat Fermented Foods (Guest Post by Tim Steele 'Tater')
• Korean Pepper Paste [B. subtilis etc] Burns Body Fat, Soil-Based Organisms (SBO), Gut Microbiota -- New Study 'Kochujang, fermented soybean-based red pepper paste, decreases visceral fat and improves blood lipid profiles in overweight adults'
• Gut I.Q. and the Distal Gut Microbiome as a Driver of Health and Disease
• Why We Are Sick and Fat: Calories In (SUPERORGANISM) = Calories Out (MICROBIOTA) + Calories Out (HUMAN) + HEAT*Fluxxx

Gut microbiota as a candidate for lifespan extension: an ecological/evolutionary perspective targeted on living organisms as metaorganisms.Ottaviani E, Ventura N, Mandrioli M, Candela M, Franchini A, Franceschi C.
Biogerontology. 2011 Dec;12(6):599-609.


Worms, Change in Hunter-Gatherer Existence and Extended Families

The second article discusses how in the Neolithic only 10,000 years ago, humans were faced with even more pathogens than ever by living in close quarters with both other humans and livestock.  Without a resilient immune system and evolving gene polymorphisms, we could not have survived.  "With the introduction of agriculture and animal husbandry, food resources became more abundant and constant and, for the first time in human history, the population size dramatically increased." The authors theorize that if it were not for improved immunity via the gut microbiota humans would not have been able to the endure the high antigenic and pathogen load.  I think this is true.  The lectins and phytates from dietary sources were one challenge and the pathogens like worms, malaria, plague, mites, and other fun things were yet another hurdle. Hemochromatosis, cystic fibrosis, increased salivary alpha-amylases might have been some of the adaptations that survived.

"The support of grandmothers in the nourishment of children allowed more pregnancies in the daughters, and thus a greater reproductive fitness."   Having two children myself, I can support their theory that post-menopausal female longevity was certainly favored for perhaps many reasons including processing grains (soaking, fermenting), preparing fermented vegetables and foods, farming and other tasks for feeding young, dependent children.  There were so many tired nights raising the little kiddies. Certainly, I would not have been able to survive the post-natal years without my children's grandparents from BOTH SIDES. LOL

"Furthermore, symbiont intestinal microorganisms provided a strategic fitness advantage for the human beings living the Neolithic agricultural revolution by protecting the host from pathogen colonization and enhancing the plasticity of the immune system. Finally, dietary change in the Neolithic agricultural societies due to agricultural practice likely induced a substantial re-adaptation of GM [gut microbiota], favouring microbial communities capable to ferment these new complex polysaccharides to short chain fatty acids (Hehemann et al. 2010)."

Who are your symbionts? Are they extinct? Do you respect them? Are you doing things that favor their growth?   Have you weeded? Seeded your gut microbiota? Feeding and breeding your symbionts in luxury and abundance?






Success Cases with SBO Probiotics and the 7-Steps
I'm grateful for Tim and Richard at FTA for starting the conversations on gut ecosystems, fiber and health optimization.  Thanks for directing people over here to the 7-Steps To Cure SIBO/SIFO.

Happy New Year to my kind readers~!!  Thank you for sharing your wonderful stories.  I love U and love hearing them all.


Case A: After 3 weeks of SBO + FIBER/RS + Gut Rehab -- Reversal of Sjogren's Auto-Antibodies (Chromatin, SSB-LA, ANA)
Anonymous was taking 3 months of PS but no changes until SBO probiotics were taken. In only 3 weeks with taking Primal Defense and Prescript Assist three times per day, she reported her autoimmune Sjogren's disease to be completely 100% 'cured'.  Three noxious auto-antibodies (SSB-LA, Chromatin, ANA) normalized or returned to near normal.

"My fingernails are clear and my cold fingers are gone. Oh, I didn't want to tell you this just yet. But my Sjogren's antibody (SSB-LA) turned negative last week! That's after being on the RS/Probiotics regimen for only 3 weeks! I was on RS since August, however. Also, one of the incipient lupus antibody that I tested positive (Chromatin) turned negative this time! My ANA is positive but with very low titer (1:40). That's the lowest I ever tested and even normal people test at that level. My rheumatologist will be confused!

If this holds up, and I'm hoping it does, I have cured an autoimmune disease. No symptoms and no antibody: that's a 100% cure. Not just remission. Being antibody-negative is not supposed to be possible, right? Whither molecular mimicry and eternal damnation, I mean, eternal autoimmune tissue attack? You mean, that's contolled by the microbiome, too? So much for Dr. Fassano and leaky gut (which I now realize seem to have been a foil ... it happens but the underlying condition seems to be gut dysbiosis and bacteria).

Wow, I gotta try this on my aunt who also has Sjogren's and my cousin who has Lupus. Thanks so much guys. This is not what modern medicine says is possible!"
--Anonymous 

Case B:  After SBO, Fermented Food + FIBER/RS + Gut Rehab -- Reversal of Pain, Poor Mood, and Fibromyalgia
From Alexander Hardy (Ajmhardy)

"Just thought I’d add to the noise here- I’ve had a set of health problems that differs from most people using RS on this site, namely persistent and intense anxiety, as well as adrenal and sleep problems due to going VLC for a few months. I’ve also had fibromyalgia for the past year now, and I could not get it to go away for the longest time. After reading Richard’s and Tim’s posts here, I added RS to my diet (which already included fermented foods, good meats, and lots of vegetables), and my symptoms have started to improve for the first time since I started feeling the pain.

They have not gone away completely yet, but my mood and the pain have gotten so much better that for the first time in a year, I completely forgot I had fibromyalgia yesterday for almost the entire day. I cannot thank you guys enough for putting in the tremendous amount of work that you do to spread the word about resistant starch... 

A note to anyone who may be reading this in hopes of helping their fibromyalgia- it took me a solid month of having dr bg.’s bionic RS and straight potato starch (total 8 TSP potato starch a day) to finally feel the pain subside, and I would guess it could take some people many months to get the same relief I got, depending on the state of their gut.

So don’t give up if this doesn’t work within a month, and make sure to include the things that I consumed before I added the potato starch- dulse (for iodine), vitamin d and K supplements, as well as N-acetylcysteine , sauerkraut, kimchi, gochujang, variety of greens and other veggies, sweet potatoes and potatoes, magnesium and zinc supplements, prescription assist, and fish oil pills."
--Ajmhardy // Dec 24, 2013 at 23:31

Case: 45 yo Female, Perfect Framingham, Perfect Cholesterol, Perfect PLAQUE PROGRESSION

When I see a female with Peripheral Vascular Disease (plaque in the legs) or angina/CAD (heart disease: plaque in the coronary arteries) or Chronic Kidney Disease (plaque in the kidney arteries)... invariably Lp(a) and low HDL2b are the PRIME factors for plaque buildup.

Another factor is a positive family history of a coronary event in the father prior to age 60 yo.



Review: Goals for Regression

Dr. Hecht has ten case studies which I will review one by one here. Earlier (Cardio Controversies: Dr. Hecht) we reviewed the success case study of the the young male with strong family CAD history, high Lp(a) and 15% EBCT regression after only 15 months on niacin 4000mg daily (and low low dose weak statin). This gentleman had regression after doubling the HDL2b from 12% to 24% and the small LDL shifted to buoyant Pattern 'A' LDL subspecies. Most notably, his Trigs started in the 200s then reduced to only 30s. O-u-t-s-t-a-n-d-i-n-g. Drugs alone? No. He must have lost weight, changed the diet, gained some body recomposition and started a good exercise program. Drugs alone cannot lower to Final Trigs 30s from the 200s. TYP goal for Trigs is 60 mg/dl however this is typically exceeded by most members especially those who are able to shift to Pattern 'A' and reach the other TYP goals. Trigs are an expression of our carbohydrates in our diet (starchy and sweet foods/beverages), saturated fats, and omega-3 fatty acids (ALA flaxseed; EPA DHA fish oil). As Trigs drop, buoyancy goes to the particles, both LDL and the HDLs. HDL-2b, the regression particle is the most buoyant, largest HDL subspecies. HDL-2b is associated with extreme longevity in centenarians, cancer-protection in remission cases and vascular regression of plaque in heart trials and at TYP.

HDL-2b are like good, loyal friends who watch out for you and your family.

Can you ever have too much?




Case Study: Perfect Scores, Perfect P L A Q U E

Dr. Hecht presents a case of a young female, no symptoms, with perfect plaque progression. She has a double-digit coronary calcification score of 95 which takes her to the top 98th percent for her age for plaque. Normal heart disease stratification at this time in conventional medicine uses the Framingham score. With her perfect baseline lipids, her score is quite good.
The Framingham 10-year risk is calculated to be < 1%.

Translation: 0-10% = 'low risk'. (10-20%=mod; >20%=high)

Her risk, in fact, is estimated to be insignificant, negligible risk.

No worries???

Yes, worry.

Alarmingly, she has the highest heart calcifications and the 'real age' of a 98 year old female.



Real Age, Real Baloney: Coronary Calcification Tells Age

Some experts Dr. Hecht discusses want to use EBCT or MDCT percentile scores as the 'real age'. This makes sense to me. It is the internal metabolic milieu, chaos and entropy which reflect our longevity and status.

Just as well, the internal metabolic calm reflect our regression and control of lifespan.



Advanced Metabolic Testing
Her results for the metabolic testing show perfect CRP (C-reactive protein). CRP is bunk. It could be elevated if you sneeze. If it is chronically elevated, then you have issues but it is no more telling of plaque than the traditional, conventional lipid panel.

On further examination, the metabolic testing which is identical to what we look at TYP program shows:
--elevated apoB (goal < 60-70)
--mildly elevated homocysteine (goal < 8.0)

Both of these indicators are related to inflammation and high carbohydrate intake. Inflammation may stem from excessive omega-6 and/or fructose, deficiencies (n-3 omegas, vitamins ADEK, B-vitamins B3 B6 B1 folate B12, minerals Magnesium Selenium Zinc Chromium Iodine Iodine, vitamin C, vitamin "O" optimism *haa*, carotenoids, mitochondrial components Carnosine CoQ10 ALCAR Carnitine; hormones adiponectin T E2 E2 P preg DHEA, etc), food allergies (wheat, gluten, A1 casein, nuts, etc), heavy metal and environmental toxicity (mercury from seafood, estrogenic pesticides, etc).





Ultimate Testing Lipoprotein Subfractionation:


The 'death band' is evident.

Recall according to Krauss, goal LDL IVb is less than zero. Just kidding, the goal is to get this subfraction which is the most dense, most lethal to as low as possible. In patients with large amounts of plaque where stenosis was > 30%, Krauss found < 2.5% of LDL-IVb was highly statistically significant for regression on angiogram. For those with 'less' plaque (read: less stable), LDL-IVb of 2.5% was still too high for regression to occur. What is good? I believe as low as possible. We see at TYP even when LDL-IVb is 1.5%, EBCT progression still occurs at 10-25%.

I don't find this acceptable.

The death band should be as low as possible. Or none.

Ultimate goal: Shift the LDL from dense to buoyant (known as LDL1 + LDL2a+b on BHL) and annihilate the 'death band'. Stop stuffing the face with fructose (fruit). Cut back olive oil and replace with some saturated fats.




Major Risk Factors for CAD: Low HDL2b, Lp(a)



Diagnosis: This young lady has extensive 98th-percentile plaque. Dense LDL, the death band LDLIVb, low HDL2b, and Lp(a).

Conventional Prognosis: No action on her doctor's part until she comes in with throbbing, painful legs or shortness of breath, back ache, jaw pain, heartburn (extensive plaque leads to vague, non-specific anginal symptoms in females). Worse case scenarios: tries to run a half-marathon or marathon and has a coronary event and is resuscitated with brain damage. Or SCD (sudden coronary death) where the first sign of heart disease is silent and fatal.
Unconventional TYP Prognosis: Longevity and shifting 98th-percentile calcifications to 15-50th-percentile less each year. Shortly... her real age will be 17 years old.

Yes, shaving YEARS off of her real age, coronary calcification percentile rank.


Hecht-Treatment: Hecht discusses niacin 4 grams per day and some statin (why? I dunno why because he contradicts himself when it comes to bashing LDL and LDL-goals; I sense some 'cognitive dissonance' on his part). Most cardiologists and physicians don't know a lick about diet, nutrition, what organs/hearts require, and basic micro- macronutrients. Didn't the father of medicine, once say 'let food be thy medicine'? We in the Paleo/Primal and TYP communities already know food can be poison (e.g. gluten, wheat, grains, legumes).

Is Hecht's therapeutic strategies enough? No. Some cases are 'treatment failures' which we'll later breakdown why.




Optimal Longevity Treatment To Reverse Vascular Dysfunction:

(1) Statin-less (statins increase Lp(a), OxLDL, OxLDL/apoB, %-dense LDL and prevent shifting from pattern B to A+++; causes autoimmunity and auto-antibodies, cellular level mitochondrial and myocyte damage, depletes antioxidants ubiquinols and coenzyme Q10; Crestor is associated with higher incidences of diabetes and kidney problems (proteinuria) in clinical trials)

(2) Niacin

(3) Omega-3 fish oil 6000++ mg EPA DHA daily for Lp(a), low HDL2b, high dense LDL, shift to pattern A, optimize n-6:3 ratio (goal ~1.5-2.0 per Dr. Barry Sears PhD and medical literature involving CKD patients)

(4) Correct Vitamin D deficiency (goal [25OHD] 60-80 ng/ml)

(5) Correct Saturated Fatty Acid Deficiency: Stop the AHA-low-fat-low-cholesterol-diet. Obtain Saturated Fats 15-20+% daily to increase HDL-2b, lower the death band LDLIVb, shift to Pattern 'A', and lower the atherogenicity of Lp(a)

(6) Correct Vitamin K2 deficiency (Sources: fermented cod liver oil, casein-free butter, hard cheeses if not allergic, natto, vitamin K2 100mcg daily MK7)

(7) Correct thyroid and adrenals by initially supporting (egg yolks, vitamins ADEK K2 Bs C; tocopherols, tocotrienols, minerals: Magnesium Selenium Zinc Chromium Iodine Iodide; saturated fatty acids, omega-3 fats ALA EPA DHA, carotenoids, avoidance of n-6 PUFAs) and if not sufficient then thyroid replacement (Armour +/- T4) and adrenal support (read HERE and HERE) to achieve optimal metabolism and stable core body temperatures 98.2 - 98.6 degrees F.

(8) Correct insulin disparities (exercise, C-A-R-B RESTRICTION, stress reduction, SLEEP, yoga, resistance train, weight loss, ketosis (diet, intermittent fasting), insulin-sensitizers: R-alpha lipoic acid, L-carnitine, Chromium, Leucine, Taurine, Glutamine, whey protein, flaxseed and fish oil, bittermelon, celery, pycnogenol, krill oil, astaxanthin, other antioxidants and proanthocyanidins, etc)

(9) Correct other calcified organ dysfunction: pineal (melatonin), hypothalamus (yoga, relaxation, breathing ex, etc), thyroid (see above), pancreas (see insulin above + digestive enzymes), gallbladder (digestive enzymes), colon (probiotics)

(10) No w-o-r-r-i-e-s ! *winky*



What about 4 grams per day of vitamin B3, niacin?

Does overdosing on niacin aid the above? Unfortunately 'no'. The mechanism of action is that niacin mimics all of the above (increases hGH, testosterone, steroids, ketosis, fasting and exercise). Adverse effects of niacin include: gout, diabetes and liver test elevations. Again I like niacin b/c it works but I don't love it. It doesn't appear to work on everyone in the year 2008-2009 and likely the future. Numerous nutritional and environmental toxicities apparently have shifted the cardiology and endocrinology playing field since the niacin trials were published, including the HATS 2001 NEJM publication by BG Brown et al.



Dr. Davis' Nutritional Wisdom and Recent TYP Topics (Members) to Reverse Vascular Dysfunction:

o Fructose: Dangerous at Any Level?
o Anthocyanidins: Eat Purple
o S-L-E-E-P -- Quality and Quantity
o Iodine Deficiency -- Importance for Heart Health
o Thermoregulation -- Thyroid and Adrenal Dysfunction
o TYP Part 3 Diet: 40% Fat Diet for Lp(a) and read more HERE

Cardio Controversies: Dr. Harvey Hecht MD

Figure 1: Correlation of metabolic factors and calcium percentile

in asymptomatic patients with EBT showed calcified plaque

(Hecht HS. Prog Cardiovasc Dis. 2003 Sep-Oct;46(2):149-70.)

Dr. Davis has known for years that assessing and treating based on the LDL-Cholesterol alone is bunk. Just as simply visually inspecting someone's physical appearance to determine their heart status is bunk. The healthiest appearing athletes may in fact have the most profound coronary artery obstructions. Similarly an asymptomatic menopausal female with exceptionally 'high' HDLs, 'low' LDL and low Trigs may also have the highest Lp(a) and peripheral vascular obstructions in the lower extremities. Heart disease is still the #1 killer of Americans and across the globe in adults. Is it a wonder why? We are not even correctly identifying asymptomatic heart disease in moderate risk individuals ((+) family history of atherosclerosis disease (heart, kidney, peripheral, cerebral, aneurysm), Lp(a), low HDL, high Trigs, Metabolic Syndrome, high fasting or post-prandial insulin, etc).

The current protocol that physicians use to score heart disease risk is called 10-year Framingham risk scoring. Recent observational studies are elucidating the complete lack of correlation between this scoring method and detection of moderate to very severe asymptomatic subclinical disease.

Framingham scoring for low or moderate risk indivuals is bunk (Nasir et al. Int J Cardiol. 2006 Mar 22;108(1):68-75.)

Complete. Utter. BUNK.

According to Nasir et al asymptomatic Brazilian men (avg age=47) who were considered low or moderate risk according to Framingham scoring, moderate to very high risk coronary calcifications were found on an EBCT scan. "...Nearly half of individuals with CACS > or = 100 (45%) and CACS > or = 75th percentile (48%) missed eligibility..." for aggressive therapy for risk reduction. CACS = coronary artery calcium scoring.




Cardio Controversies: Dr. Harvey Hecht MD

Dr. Hecht was one of the cardiologists who has worked closely with Superko and Krauss over the last 10-20 yrs on statin trials, subfractionation of lipoproteins and more recently interventional radiology involving EBCT and MDCT. Like Callister (recall, Cardio Controversies HERE), Hecht originally saw a decline in EBTC coronary calcifications with statin monotherapy in one single study, however he could not be replicated the results at later dates. Like Krauss and Callister, he has questioned why this is the case. In a 2003 publication, he reviews the importance of many concepts that characterize our TYP program (Hecht HS. Prog Cardiovasc Dis. 2003 Sep-Oct;46(2):149-70. Free PDF HERE). Obviously, our TYP program embraces a program that is far and beyond conventional statin+niacin-centric therapy: diet, lifestyles, exercise, nutraceuticals, and no pharmaceuticals (excluding niacin and fish oil). Hecht's approach is basically mega doses of niacin niacin and more niacin (+low dose weak statin), which is quite fine but not very targeted or tolerable to most and fails to address the metabolic origins of heart disease, obesity, MetSyn, diabetes and inflammation.



LDL-Cholesterol Alone Tells Nothing

One of Dr. Hecht's first assertions is that LDL-C is completely, fully, unrelated to subclinical and clinical coronary calcifications. See above diagram, Figure 1. The R correlation quotient between LDL-C and positive coronary calcification was 0.0006 (p=0.90). To quote my favorite THINCer, Peter, 'count the ZEROES.' *ha*

Utterly. Unrelated.



Metabolic Parameters Matter

The highest correlations between overall plaque burden and measurable lipoprotein parameters were LDL peak particle diameter in angstroms, R = 0.14, P = .02 and high-density lipoprotein cholesterol, R = 0.11, P = .02). Of course these R values are not great since optimal statistically is 0.80 but this is the closest relationship determined from countless EBCT scans and patient datasets. In other words, Pattern 'A' versus Pattern 'B' makes a big difference, even a little more than how much HDL there is.

Figure 8. Correlation of annualized progression
of calcium score and change in metabolic factors.

C h a n g e in Plaque Burden Correlates Best With Small Dense LDL Changes

Hecht continued to examine how changes in the metabolic parameters related to change in coronary calcifications as visualized and quantitified by EBCT. The best relationship was found between percent change in Small Dense LDL (IIIa+b subfractions). Not HDL improvements (he apparently didn't look at HDL2b). Not Trig improvements. Definitely not LDL-C improvements (again, don't forget to count the zeroes,
R = 0.009, P=0.91). Not even the TC/HDL ratio improvements.

Regression or progression in coronary calcifications was highly associated with changes in sd-LDL out of ALL the parameters tested (R=0.46, p=0.71). See above. We see these correlations at TYP as well. Regression is highly associated with
--control of sd-LDL to < 10-30%
--annihilation of the 'death band' LDL-IVb from > 5% to as low as possible < 1-2 %
--solid Pattern 'A'
--increasing HDL-2b to as high as possible 60-200%


Our members do regression with DIET. LIFESTYLES. Supplements (omega-3, phosphatidylcholine, vitamin D, etc). LOW DOSE niacin 1-2 grams per day. STATIN-LESS... or on the way to statin-less.





High-Saturated Fat Diet Improves ALL Metabolic Metrics

These metabolic metrics -- sdLDL and HDL2b -- according to Krauss' research on lipoproteins are related mostly to (1) dietary saturated fatty acid intake (2) dietary carb loads.

Let's summarize Dr. Krauss' high fat study once more and then see how it compares in the context of CACS regression in an extremely high risk CAD patient whose father had an MI at age 46 (Case study #8; Figure 16). The carb intake again in Krauss' study is considered high by many standards at 39% and not as effective in lower small dense LDL or raising HDL-2b as lower carb or very low carb (VLCD) diets in insulin resistant individuals. Interesting comparisons can still be made.

Summary of Heart-Healthy Improvements with a High-Saturated Fat (18%) Diet in only Six Weeks:

(1) Increased total HDL-Cholesterol 18% (baseline 42 mg/dl)
(2) Increased Regression subspecies HDL-2 of 50%(3) Reduced Triglyercides by 30% (baseline 141 mg/dl)
(4) Increased total LDL-Cholesterol by 13% (good thing b/c LDL-diameter incr)
(4) Decreased LDL-IIIa+b from 27% to 18%(5) Decrease LDL-IV from 6.0% to 3.4%

Figure 16. Case 8. Metabolic data and EBT images

before and after 14 months of statin and niacin

combination therapy in a 47-year-old man with a

baseline calcium score of 442 in the 97th percentile.

Regression Case Study in a High CAD RISK Individual:
EBCT CAC Reduction 15% Annualized

This 47 yo patient's (see above) therapy included ultra high dose niacin (equivalent to 8 tablets of OTC Slo-Niacin 500mg) which was a dose similarly used in the HATS regression trial, plus low dose weak potency statin. His CAC score put him at the highest 97-percentile of extremely high coronary risk. His father had suffered an acute myocardial infarction at age 46.

What is quite notable with this regression case is the rapid changes in multiple metabolic parameters esp Lp(a) with niacin. Niacin is one of the few therapies that successfully lowers Lp(a). In the HATS trial ~20% of men and ~30% of women had elevations of Lp(a). High dose niacin worked for this gentleman with the tremendous plaque burden. In the EBCT scan, the reduction in LAD was obvious the author stated. See above.

Recall what does niacin mimic? Niacin binds the ketone body receptors which are activated during many of the strategies employed by TrackYourPlaque members:
--intermittent fasting ('fastest way to control plaque')
--carbohydrate restriction
--mod-high protein diet (Primal, Protein Power, phases 1-2 of South Beach)
--mod-high fat diet (TYP Diet Part 3, Primal, Protein Power, low carb high fat Paleo)









Metabolic Parameters Improved

Can we achieve similar multiple metabolic parameter improvements with diet + lifestyles alone?

Faster?

Without drug or ultra high dose niacin side effects?

How would ultra high dose 15 months of Niacin 4000 mg + statin daily in a 47 yo asymptomatic male compare with 6 weeks DR. Krauss' high fat diet in n=103 healthy men (46% fat, 18% sat fat when compared with AHA-Walter-Willet-low fat 8% sat fat)? Granted it is hard to make comparisons between Krauss' healthy study participants and this asymptomatic CAD Case Study, the baseline values for lipoproteins were not that significantly dissimilar from this Case Study (Low HDL, higher TG).

Very similar endpoints in fact can be achieved V E R Y rapidly!

The primary parameters to compare are:

High Fat x 1.5 months:
** Increased Regression subspecies HDL-2 of 50%
** Decreased LDL-IIIa+b from 27% to 18%
** Pattern 'A' to 'A+++' (LDL diameter from 25.9 to 26.5nm)

Pharmacotherapy x 15 months:
** Increased Regression subspecies HDL-2b of 71%** Decreased LDL-IIIa+b from 34.1% to 18.6%
** Pattern 'B' to 'A+++' (LDL diameter from 24.9 to 26.6nm)

Lp(a) Reduced By Saturated Fatty Acids and Raised by Low-Sat-Fat Diets
Benefits of Krauss high-saturated fat diet cannot be overstated. Saturated fats control CETP and thus control the amount of Lp(a) individuals produce. In fact, when an experiment group was put on a low fat, high veggie diet, Lp(a) increased significantly by as much as 9% (Silaste ML et al Arterioscler Thromb Vasc Biol. 2004 Mar;24(3):498-503. Free PDF HERE .)

Additionally, the low fat diet produced HIGHER oxidized LDL (OxLDL) by 27%. Recall the small dense LDL are less resistant to oxidation than buoyant large LDL and transform to OxLDL rapidly.

Not good.

For. Plaque. Burden.

OxLDL causes fatty/calcified organs: arteries (atherosclerosis); endothelium (hypertension); liver (NASH); pancreas (diabetes, MetSyn); thyroid (Hashimoto's), visceral fat (obesity); etc.


Saturated fat lowers and controls Lp(a) and coconut oil is one great example (Muller H et al . J Nutr. 2003 Nov;133(11):3422-7. Free PDF HERE). In this study by Muller et al women with elevated Lp(a) in the 30s mg/dl were provided a coconut oil-rich diet (22.7% sat fat; 3.9% PUFA) was compared with a high PUFA-diet (15.6% PUFA !!yikes). Lp(a) was reduced 5.1% compared to baseline habitual diets with the high saturated fat diet whereas in the high PUFA diet, Lp(a) increased a whooping 7.5%. The difference between Lp(a) on the high sat fat compared to the high PUFA diet was 13.3%.

[Coconut oil is great unless one is allergic. I am aware of a friend allergic to both olives + oil and coconuts + oil. Dr. Hyman discusses food allergies and how to determine what they are via an elimination diet HERE to control inflammation and reduce autoimmunity.]



References

Hecht HS, Superko HR. Electron beam tomography and National Cholesterol Education Program guidelines in asymptomatic women. J Am Coll Cardiol. 2001 May;37(6):1506-11.

Nasir K, Santos RD, Roguin A, Carvalho JA, Meneghello R, Blumenthal RS. Relationship of subclinical coronary atherosclerosis and National Cholesterol Education Panel guidelines in asymptomatic Brazilian men. Int J Cardiol. 2006 Mar 22;108(1):68-75.

Santos RD, Nasir K, Tufail K, Meneghelo RS, Carvalho JA, Blumenthal RS. Metabolic syndrome is associated with coronary artery calcium in asymptomatic white Brazilian men considered low-risk by Framingham risk score. Prev Cardiol. 2007 Summer;10(3):141-6.

Campbell CY, Nasir K, Carvalho JA, Blumenthal RS, Santos RD. The metabolic syndrome adds incremental value to the Framingham risk score in identifying asymptomatic individuals with higher degrees of inflammation. J Cardiometab Syndr. 2008 Winter;3(1):7-11.

Superko HR. Small, dense, low-density lipoprotein and atherosclerosis. Curr Atheroscler Rep. 2000 May;2(3):226-31.

Superko HR, Hecht HS. Metabolic disorders contribute to subclinical coronary atherosclerosis in patients with coronary calcification. Am J Cardiol. 2001 Aug 1;88(3):260-4.

Hecht HS, Superko HR, Smith LK, McColgan BP. Relation of coronary artery calcium identified by electron beam tomography to serum lipoprotein levels and implications for treatment. Am J Cardiol. 2001 Feb 15;87(4):406-12.

Anand DV, Lim E, Raval U, Lipkin D, Lahiri A. Prevalence of silent myocardial ischemia in asymptomatic individuals with subclinical atherosclerosis detected by electron beam tomography. J Nucl Cardiol. 2004 Jul-Aug;11(4):450-7.

Rumberger JA. Cost effectiveness of coronary calcification scanning using electron beam tomography in intermediate and high risk asymptomatic individuals. J Cardiovasc Risk. 2000 Apr;7(2):113-9. Review.

Coylewright M, Blumenthal RS, Post W. Placing COURAGE in context: review of the recent literature on managing stable coronary artery disease. Mayo Clin Proc. 2008 Jul;83(7):799-805.

Grundy SM. Coronary calcium as a risk factor: role in global risk assessment. J Am Coll Cardiol. 2001 May;37(6):1512-5. Review.

Hoff JA, Daviglus ML, Chomka EV, Krainik AJ, Sevrukov A, Kondos GT. Conventional coronary artery disease risk factors and coronary artery calcium detected by electron beam tomography in 30,908 healthy individuals. Ann Epidemiol. 2003 Mar;13(3):163-9.

Budoff MJ, Gul KM. Expert review on coronary calcium. Vasc Health Risk Manag. 2008;4(2):315-24.