Hypertension and the X-Image

From the left: Mechad Brooks (from True Blood), Spanish tennis player Fernando Verdasco and Japanese soccer player Hidetoshi Nakata.

How is the X-Image and Hypertension Related?

[This is not a stretch... *wild wink*]

For men, this is the balanced, broad shoulders, narrow hips image. For women, strong symmetrical shoulders, narrow waist, wide child-bearing hips, long gams. The X-look was coined by Prof DeVany. Evolutionarily, secondary sex traits are associated with high fertility. For both genders, a narrow waist signifies high hormones -- testosterone (not hair-losing-DHT), estrogen, progesterone, DHEA, pregnenolone, etc. And... Low insulin, low insulin resistance and low inflammation and, thus, high immunity and resistance to lethal infections, the biggest killer of ancestral man besides predators and famine/drought.

Low insulin and low insulin resistance also corresponds (typically) to no visceral fat (intra-abdominal adiposity)... and narrower waists, precisely, the X-image.

Many genetic adaptations derive to push forward genetic material to the next generation and to provide for a stronger immune surveillance and protection system. Peter will soon be discussing the (protective) role of Lp(a) and the evolutionary disadvantages of vegetarianism. Bantu vegetarians not only have higher Lp(a) but also higher blood pressures.



Brain, Neuropeptides, and Hormones

The primary controller of fertility and sexual function is our... BRAIN.

I am not joking. Indeed, the brain is our biggest sex organ.

The pituitary-gonadal axis influence sex hormones and fertility by incorporating multilevel inputs from the intestines/GI, muscles, senses (eyes, ears, mouth/ philematology, smell/ pheromones), fat stores, liver, etc .

Scheider JE discusses the balance of energy and reproduction thoroughly. Two diagrams are from Energy Balance and Reproduction, click for PDF HERE.



Energy Balance and Reproduction

The physiological mechanisms that control energy balance are reciprocally linked to those that control reproduction, and together, these mechanisms optimize reproductive success under fluctuating metabolic conditions. Thus, it is difficult to understand the physiology of energy balance without understanding its link to reproductive success. The metabolic sensory stimuli, hormonal mediators and modulators, and central neuropeptides that control reproduction also influence energy balance. In general, those that increase ingestive behavior inhibit reproductive processes [e.g. excessive carbohydrates], with a few exceptions. Reproductive processes, including the hypothalamic–pituitary–gonadal (HPG) system and the mechanisms that control sex behavior are most proximally sensitive to the availability of oxidizable metabolic fuels. The role of hormones, such as insulin and leptin, are not understood, but there are two possible ways they might control food intake and reproduction. They either mediate the effects of energy metabolism on reproduction or they modulate the availability of metabolic fuels in the brain or periphery.

This review examines the neural pathways from fuel detectors
to the central effector system emphasizing the following points:

0 First, metabolic stimuli can directly influence the effector systems independently from the hormones that bind to these central effector systems. For example, in some cases, excess energy storage in adipose tissue causes deficits in the pool of oxidizable fuels available for the reproductive system. [Recall, insulin stores/locks in fat. We need 'some' insulin for muscle growth, but really not much. Hard-gainers have insulin resistance in the liver and elsewhere, I strongly suspect.] Thus, in such cases, reproduction is inhibited despite a high body fat content and high plasma concentrations of hormones that are thought to stimulate reproductive processes. The deficit in fuels [fatty acid fuel deficits caused by carb-pathways turned on] creates a primary sensory stimulus that is inhibitory to the reproductive system, despite high concentrations of hormones, such as insulin and leptin.

o Second, hormones might influence the central effector systems (including gonadotropin-releasing hormone (GnRH) secretion and sex behavior) indirectly by modulating the metabolic stimulus.

o Third, the critical neural circuitry involves extrahypothalamic sites, such as the caudal brain stem, and projections from the brain stem to the forebrain. Catecholamines [adrenaline, stress], neuropeptide Y (NPY) and corticotropin-releasing hormone (CRH) are probably involved.

o Fourth, the metabolic stimuli and chemical messengers affect the motivation to engage in ingestive and sex behaviors instead of, or in addition to, affecting the ability to perform these behaviors. Finally, it is important to study these metabolic events and chemical messengers in a wider variety of species under natural or seminatural circumstances.

Insulin and Leptin 101 Basics

For more insulin and leptin 101 basics, please see Dr. A, my soul sister in science *BIG SMILE!*
--Mastering Leptin book report (but note her '????'s where I think she politely says wtf)

Stiffness. Caused by Insulin and ROS.

OK sometimes we want stiffness.

Er... But not forever...

Like a rubber tubing left outside to the elements, the vascular system in mammals (and fish) will stiffen and crack if it loses contractility and elasticity from oxidative damage. Rubber is resilient, yielding and flexible until it starts to break down from damaging factors such as UV, heat, cold, salt, oxidation, radiation, etc. In biologic systems, unlike rubber, there is respite and forgiving repair. Damage only occurs when the destructive factors outpace the rate of repair. The coronary arteries are most affected due to narrow relative diameters and high shearing forces as blood is pumped from the heart to the peripheral tissues. The higher the pressure, the more potential damage to the endothelium (lining of blood vessels). As the body tries to heal these tiny 'nicks' in the endothelium, scar tissue and calcifications form. If the immune system is on abnormal 'hyper-overdrive' or if the BP is abnormally high, then the scarring and calcifications can be more extensive, more keloidal, more thick with plaque. Those with Lp(a) (at any level, according to Dr. Harvey Hecht's research) tend to over-scar, it appears when the Lp(a) particles are small and oxidizable. Don't be dense. Saturated fat increases the size of LDL as well as Lp(a) (which is just LDL plus apo(a)), which improves the buoyancy and anti-atherogenic properties of LDL and HDL.





Insulin, Insulin Resistance Raise BP and Coronary Calcifications

High blood pressure is a 'gateway' condition to heavier, harder, stiffer conditions. BP greater than 110/70 is one of the first indicators that something is going on... See prior Nephropal post: Insulin.

BP is reflective of our inflammatory status and health of the endothelium. What causes BP to rise? Well. If you ask a cardiologist or any primary doc, they will tell you that essential hypertension has no known cause. WTF. With going paleo, BP, insulin, and insulin resistance are all lowered. Frasetto et al at UCSF showed this (as well as EVERYONE in the paleo community who was previously ill). Click HERE prior nephopal. With going low carb, Meckling et al has shown that BP, insulin and glucose were all also lowered (click HERE).

In the low-fat arm, of course, this was not the case. Low-fat is killing America by raising and maintaining high insulin levels which make us fat and STIFF.

Dr. Houston has discussed known causes of hypertension: ROS (reactive oxygen species), e.g. inflammation. Nephropal post: Nutrigenomics and Hypertension.

o Blood pressure and fasting plasma glucose rather than metabolic syndrome predict coronary artery calcium progression: the Rancho Bernardo Study.

o Insulin resistance independently predicts the progression of coronary artery calcification.

o Adiponectin, visceral fat, oxidative stress, and early macrovascular disease: the Coronary Artery Risk Development in Young Adults Study.

o Psychological stress, insulin resistance, inflammation and the assessment of heart disease risk. Time for a paradigm shift?

o Relationship of adiposity to subclinical atherosclerosis in obese patients with type 2 diabetes.




What Does NOT Raise Insulin?

Fat.

Pure unadulterated fat.

I aint talking olive oil honey.

See prior animal pharm: Insulin and Aging -- how low carb, high saturated fat works.


What Raises Insulin?

--Dietary carbohydrates (e.g. oatbran, grains, corn, legumes)
--(protein, mildly)
--Fructose
--Omega-6
--Gluten (via both the carb route and the endorphin system)
--Cortisol (stress, sleep deprivation, endurance training, etc)
--Hormone deficiencies (vitamin D, testosterone, estrogen, omega-3 fish flax, thyroid, etc)
--Drugs (steroids, birth control, Crestor/ rosuvastatin, Provera/ progestins, water pills, etc)
--Lack of ketones (MCT oil, coconut oil, periodicity of exercise or fasting)
--Sedentary atrophying lifestyle
(Last X-Image: Kellan Lutz, from Twilight series and 90210)



Dr. T's Winterization (good) v. Over-Summerization (bad)

Diagram from Schneider, modified.

Benefits of High-Saturated Fat Diets (Part IV): REGRESSION IN HEART PATIENTS

Few studies review the benefits of high-saturated fat diets in actual heart disease patients. Perhaps, researchers worry about... M A L P R A C T I C E . . . ?

Like urban myths, do such studies exist?

Indeed studies of high saturated fat diets in heart disease patients IN FACT do EXIST.

LA...la la la... I feel on top of the world... (LMFAO)


The diagram exemplifies a normal coronary artery, with a large.. wide diameter... spacious... flexible.. lumen (Courtesy: medicinenet.org). The diameter of the artery can be measured accurately down to fractions of a millimeter via angiography.

It was observed that in post-menopausal women with documented heart disease from the Estrogen Replacement and Atherosclerosis (ERA) trial, a multicenter clinical trial evaluating the effects of hormone replacement therapy on atherosclerotic progression, in the group consuming the highest-saturated dietary fat diet (12.0% Sat Fat), an enlargement in coronary diameter of 0.01 mm and a 0.1% regression in coronary artery stenosis.

Quoted to Men's Health, "In the nutrition field, it's very difficult to get something published that goes against established dogma," said Dr. Dariush Mozaffarian MD MPH, assistant professor, Harvard. "The dogma says that saturated fat is harmful, but that is not based, to me, on unequivocal evidence." Mozaffarian says he believes it's critical that scientists remain open minded. "Our finding was surprising to us. And when there's a discovery that goes against what's established, it shouldn't be suppressed but rather disseminated and explored as much as possible."

In a year during my pharmacy student training at Stanford, I worked with Dariush on an internal med rotation for 4wks. I think I learned more about drugs and how to use them than some of my preceptors combined. His teaching approaches were usually articulate, concise and patiently provided. Gosh, can I say, I've had serendipity with many mentors in my little drug journey so far. *haa*

• Dietary fats, carbohydrate, and progression of coronary atherosclerosis in postmenopausal women. PDF click HERE. Mozaffarian D, Rimm EB, Herrington DM. Am J Clin Nutr. 2004 Nov;80(5):1175-84. EDITORIAL. Figure 1 below.
  

Dividing the saturated fat intake into quartiles, the individuals at the highest quartile (dietary saturated fat intake: 12.0%) demonstrated the least progression on angiogram of coronary diameter. In fact, this was the only group that exhibited REGRESSION.

This group was also characterized as having the:
--least medications, including lipid-lowering medications
--the least medications and the higher the saturated fat, the more coronary artery widening in coronary artery diameter
--highest LDL (low density lipoprotein) measurements
--highest HDL (high density lipoprotein 'good cholesterol)
--highest HDL2 (the regressive particle)
--lowest Trigs
--MOST PAST AND CURRENT SMOKERS
--highest dietary fat intake (32%)
--highest monounsaturated fat intake
--lowest dietary carbohydrate intake (47.1% v. (!!) 69%)



Improved Anti-Atherogenic Lipoproteins
"A higher saturated fat intake was associated with a more favorable lipoprotein profile, including higher HDL,HDL2, and HDL3 cholesterol; higher apoprotein A-I; lower triacylglycerolc oncentrations; and a lower ratio of total cholesterol(TC) to HDL cholesterol (TC:HDL cholesterol). Women who consumed more saturated fat consumed less carbohydrate and dietary fiber and more total fat, protein, cholesterol, polyunsaturated fat, trans fatty acids, and monounsaturated fat."



Lipid-Lowering Drugs: The Less, The More Regression
The researchers astutely noticed that "among the women not taking lipid-lowering medication at baseline or during follow-up, there was 0.22 mm less progression for each 5% greater energy intake from saturated fat, compared with 0.09 mm less progression for each 5% greater energy intake from saturated fat among women taking lipid-lowering medication (P = for interaction 0.008)."


Omega-6 PUFAs: Highly Associated with Progression
After the Lyon-Diet Heart trial was completed and showed a dramatic reduction in all-cause mortality, cardiac death and events with simple reductions in omega-6 PUFAs and increase omega-3 from fish and ALA sources like olive oil, I think this trial hits it home again that any increase in dietary PUFAs are extremely pro-inflammatory leading to progression of coronary artery diameter reductions. The lowest quartile consumed less than 3.9% PUFA which was positively (see above) associated with less of a decline of average minimal coronary artery diameter (P for trend =0.04) compared with other quartiles. Clearly, a dietary PUFA concentration greater than 3.9% was highly statistically correlated to angiogram progression. The highest quartile that consumed 7.5% PUFA in the diet this was shown to produce the second highest amount of artery diameter constriction in this trial.

FIGURE 1 (divided, above, below). Mean (SE) change in minimal coronary artery diameter according to intake of different nutrients, with adjustments as in Table 2 (see footnote 1), except that total fat was not adjusted for carbohydrate, and carbohydrate and protein were also adjusted for polyunsaturated fat. These models estimate the effect of saturated fat replacing other fats (monounsaturated or polyunsaturated),monounsaturated fat replacing other fats (saturated or polyunsaturated), polyunsaturated fat replacing other fats (saturated or monounsaturated), total fat replacing carbohydrate, carbohydrate replacing saturated or monounsaturated fat, and protein replacingsaturated or monounsaturated fat.

Median intakes(% of energy) for quartiles 1–4 were as follows:
saturated fat*** (6.1, 7.8, 9.5, and 12.0),
monounsaturated fat (6.9, 8.6, 10.7, and 13.0),
polyunsaturated fat** (3.9, 5.2, 6.1, and 7.5),

total fat (17.6, 21.7, 27.0, and 31.9),
carbohydrate* (47.1, 55.6, 60.5, and 68.9)
protein (12.7, 15.8, 18.0, and 21.2).

P for trend = 0.001 (**saturated fat), 0.40(monounsaturated fat), 0.04 (**polyunsaturated fat), 0.48 (total fat), 0.20 (protein), and 0.001 (*carbohydrate).

High Carbohydrate Intake: Associated with Coronary Plaque Progression
The authors also found that "Carbohydrate intake (see above) was strongly positively associated with progression, with a 19-mm greater decline in mean minimal coronary artery diameter in a comparisonof extreme quartiles of intake (P for trend = 0.001)."


Overview
The design of this particular study was novel in examining multiple dietary components against a validated heart disease marker for progression. Obviously, prospective RCTs utilizing high-saturated fat, low carb, low PUFA diets would constitute the best scenarios to show unequivocal heart disease reversal. Am I going to hold my breath?



R e g r e s s i o n
With a high-saturated fat diet in documented heart disease patients... coronary artery stenosis regression occurred shockingly in individuals who took less lipid-lower drugs, smoked more, and basically were hedonistic beyond a conventional cardiologist's belief. Should we live life a little dangerously... disobey the 'rules'?

Bone Marrow: Immunoprotective and Improves Endothelial Dysfunction

Chicken Soup. Do you love it?

Why?

Do you know scientifically and medically why it's so beneficial and therapeutic (better than a FLU SHOT)?



What satisfies the soul and combats colds, infections and vascular atherosclerosis (CAD, PVD, PAD, CVD, CKD)?

Bone marrow derived endothelial progenitor cells (EPCs)!!! From bone marrow.

(preferable organic, 80%+ grassfed, from Whole Foods or a reputable ranch)

Pharmacological approaches to improve endothelial
repair mechanisms.
Besler C, Doerries C, Giannotti G, Lüscher TF, Landmesser U.
Expert Rev Cardiovasc
Ther. 2008 Sep;6(8):1071-82. Review.
PMID: 18793110

Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland.

Endothelial injury is thought to play a pivotal role in the development and progression of vascular diseases, such as atherosclerosis, hypertension or restenosis, as well as their complications, including myocardial infarction or stroke. Accumulating evidence suggests that bone marrow-derived
endothelial progenitor cells (EPCs) promote endothelial repair and contribute to ischemia-induced neovascularization. Coronary artery disease and its risk factors, such as diabetes, hypercholesterolemia, hypertension and smoking, are associated with a reduced number and impaired functional activity of circulating EPCs. Moreover, initial data suggest that reduced EPC levels are associated with endothelial dysfunction and an increased risk of cardiovascular events, compatible with the concept that impaired EPC-mediated vascular repair promotes progression of vascular disease. In this review we summarize recent data on the effects of pharmacological agents on mobilization and functional activity of EPCs. In particular, several experimental and clinical studies have suggested that statins, angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor blockers, PPAR-gamma agonists and erythropoietin increase the number and functional activity of EPCs. The underlying mechanisms remain largely to be defined; however, they likely include activation of the PI3-kinase/Akt pathway and endothelial nitric oxide synthase, as well as inhibition of NAD(P)H oxidase activity of progenitor cells.

The above seminal article suggests that bone marrow may hold the key to improving endothelial problems and inflammation. The astute authors suggest the below pharmaceuticals would be helpful. What are the food analogues if we had to 'deconstruct' these drug components they allude to? Would food be safer? Better? More efficacious? Yes... I belive so. Not just because your momma made it! :)

--Statins: How about fish oil? how about veggie-fibers? how about chol/sat fats? How about plant sterols (like in butter oil)?
--Angiotensin-converting enzyme inhibitors: How about Taurine, L-Arginine (like contained in nuts and seafood/meat?)? how about other essential proteins glutamic and aspartic acid, lysine, hydroxylysine and histidine?
--Angiotensin II type 1 receptor blockers: How about Glycine, Taurine?
--PPAR-gamma agonists: How about high dose EPA DHA fish oil ALA/flaxseed oil? how about Taurine/Leucine proteins? how about exercise/ IF/ starving occasionally? sat fats? how about CLA (like in meat and butter oil)? how about meat-derived Carotenoids which synergize PPAR effects? how about Lutein/eggs? Astaxanthin? Krill oil?
--Erythropoietin: How about eating b o n e m a r r o w ?


Essential fatty acids and their metabolites could function as endogenous HMG-CoA reductase and ACE enzyme inhibitors, anti-arrhythmic, anti-hypertensive, anti-atherosclerotic, anti-inflammatory, cytoprotective, and cardioprotective molecules.
Das UN.
Lipids Health Dis. 2008 Oct 15;7:37. Review.
PMID: 18922179

Peroxisome proliferator-activated receptors mediate pleiotropic actions of statins.
Paumelle R, Staels B.
Circ Res. 2007 May 25;100(10):1394-5. No abstract available.
PMID: 17525375


What does Bone Marrow contain which is so nutrient dense and fabulously fantastic?
--EPA + DHA
--Hormones: Testosterone, Estrogen, Progesterone, Human Growth Hormone
--Vitamin A D E K
--EPO (erythropoitin)
--Minerals: Magnesium, Calcium, Zinc, etc
--Saturated Fats
--Proteins: L-Arginine (which lowers BP in pre-eclampsic women), Glutamate, Aspartic acid, Lysine, Hydroxylysine and Histidine
--EPCs (endothelial progenitor cells) which improve our BLOOD VESSELS and promote better CIRCULATION AND BLOOD FLOW and healthier endothelium
--Serotonin, mood neurotransmitter (yes, SSRI antidepressants are highly associated with osteoporosis and nonvertebral fractures as we 've recently learned HERE and HERE and HERE); some people reported getting 'high' on bone marrow like marine biologist Dr. Dan, perhaps this is why? Marrow Madness and Its Hidden Secrets


Wow. My cat who can eat whole mice and their lovely bones knows what she's doing!

Peter's fans (eg, Anna of Against the Grain) have listed optimal bone feeding of cats HERE.