Monday, July 19, 2010

Meat Science: Meat and Omega-3 as ACE-Inhibitors

T. Colin Campbell: No Longer Pied-Piper?

So... Again the data speaks volumes and the diminutive Ms. Mingers has put the final dagger in the vegetarian-low-sat-fat-fairy tale spun by so-called academic Campbell. The action is here: The China Study, My Response by Denise Minger.

You know if my teeth, eye color and health were ruined by a low saturated fat, low cholesterol, no meat, high soy, high grain vegetarian diet... I'd be mildly pissed.

And hungry...

For M-E-A-T . . . !



Meat Science

Added to NCBI PubMed in Feb, this newer journal features research and science in MEAT. I came across two articles here regarding protein from meat and beef which behave as ACE-inhibitors, one of the drugs deployed for hypertension, afterload reduction in heart failure and kidney protection in Type 1 (T1)and Type 2 diabetes (T2D) individuals. The mechanism of action of these drugs is blocking a pro-inflammatory-associated enzyme known as angiotension converting enzyme, ACE. Many peptides (proteins that are short sequences) are found in animal, seafood and plants that we consume that, in fact, have ACE-inhibitory action in mammalian systems. Even breastmilk contains lactoferrin which may inhibit ACE.

(1) A review of meat protein hydrolysates and hypertension.
Ahhmed AM, Muguruma M.
Meat Sci. 2010 Sep;86(1):110-8.

(2) Purification and identification of angiotensin converting enzyme inhibitory peptides from beef hydrolysates
A. Jang and M. Lee
Meat Science, Volume 69, Issue 4, Pages 653-661.


Clinical M-E-A-T Series *haa*:
o Meat as Medicine: Grassfed v. Conventional
o Phytanic Acid in Grassfed Meat: Binds PPAR-α and RXR (potent anti-inflammatory controls)


Other related meat science and research:
o Antihypertensive Activities of Peptides Derived from Porcine Skeletal Muscle Myosin in Spontaneously Hypertensive Rats
o Novel Angiotensin-Converting Enzyme (ACE) Inhibitory Peptides Derived from Boneless Chicken Leg Meat
o Antihypertensive effects and endothelial progenitor cell activation by intake of chicken collagen hydrolysate in pre- and mild-hypertension. [Endothelial progenitor cells are required for cellular and organ regeneration -- prior animal pharm Chicken Soup, Bone Marrow, and EPCs for organ regeneration]




Complex Chronic Diseases and ACE/AII Activity

Diseases since the DAWN OF TIME typically involve stress (physical, mental), trauma, infection, hormone imbalances, omega-3/omega-6 imbalances and elevated insulin, are associated with elevated ACE and AII activity. ACE is a membrane-bound peptidyl dipeptidase known to act on a variety of protein substrates in the extracellular space. Known functions are the formation of angiotensin II and the degradation of bradykinin. ACE has an indispensable role in animal physiology: aids in maintaining homeostasis and preventing death during duress activated by mammalian 'fight or flight', our hard-wired mechanism for survival. A sharp cascade of neuroendocrine and circulatory chemicals are released in stressful/imbalanced situations, as the body is trying to keep blood flow to the brain, heart and vital organs, heart pumping activity and other vital processes (see below diagram). ACE catalyzes the conversion from (less active) Angiotensin I to (more active) Angiotensin II. Do we require ACE and Angiotensin II? Of course, this system required to clear damaged tissue, maintain perfusion of tissues and organs and activate the immune system for healing after trauma and infection. Tourgeman discusses the role of Angiotension II here: ' (a) increases pressure within the kidneys, (b) increases fibrosis (scarring), (c) increases the recruitment of pro-inflammatory white blood cells, (d), increases the production of inflammatory cytokines (chemicals), and (e) increases cell proliferation.'





Controlling Insulin, ACE and AII

Epinephrine (adrenaline), norepinephrine, cortisol, renin, aldosterone and other adrenal gland secretions are prompted acutely on a short-term basis. Under high insulin and chronic conditions, these powerful adrenal hormones and chemicals are inappropriately turned on long-term.

Any studies?

Frassetto et al (EJCN, 2009) showed that pre-hypertension normalized after 10 days on a hunter-gather paleolithic diet (grain-free, legume-free) in overweight men and women aged 18+ yo. This study was superby in reducing HOMA, insulin resistance, and basal insulin secretion by ~70%.

Subsequently, the systolic blood pressure reduced by 2.6 mmgHg (NS) diastolic blood pressure dropped from 71 by 3.1 mmHg (p=0.006); this is of huge magnitudes greater than those produced in the VAST MAJORITY of clinical anti-hypertensive drugs.

In younger patients the diastolic BP is more difficult to modify and lower; flips as we get older and arteries stiffen up.

A broad Cochrane review found "We found 92 trials that randomly assigned participants to take either an ACE inhibitor or an inert substance (placebo). These trials evaluated the blood pressure lowering ability of 14 different ACE inhibitors in 12 954 participants. The trials followed participants for approximately 6 weeks (though people are typically expected to take anti-hypertension drugs for the rest of their lives). The blood pressure lowering effect was modest. There was an 8-point reduction in the upper number that signifies the systolic pressure and a 5-point reduction in the lower number that signifies the diastolic pressure."

Again in the hunter-gatherer paleolithic diet (granted they were not yet hypertensive, but on the road there), IN ONLY DAYS of diet modification achieved statistically significant blood pressure reduction.

On this evolutionary/paleo diet, treatment participants consumed eggs, M-E-A-T, or seafood at EVERY MEAL.

Harmful?

No.

Healing.

And frequently and highly observed in individuals who lower their insulin levels and adopt an anti-inflammatory evo/paleo diet (and if necessary take antioxidants like omega-3, zinc, magnesium, etc).



Pharmaceuticals Do Not Work

IMHO ACE-inhibitor and ARB pharmaceuticals hardly at all or only marginally improve chronic disease processes. Unlike food components, drugs are strong. Artificial substances foreign to mammalian systems (xenobiotics) are not metabolized and eliminated in the same fashion as food components thereby potently binding and staying around quite a long duration. Besides binding one single receptor, they may inevitably activate or inhibit a vast variety of other interrelated receptor/enzyme systems. That is how we are built. Everything is INTERRELATED. Approximately 17% of users of an ACE-inhibitor report a dry, non-productive cough as a result of bradykinins building up which cause inflammation in the lungs, consequently resulting in an asthma-related cough. Captopril is the least because it does not affect bradykinin expression as much.

Dry, high-bradykinin, annoying, lingering, inflammation-related cough in affected ACE-inhibitor drug-users? Good? Probably not despite purported 'benefits'.

Another adverse effect of ACE-inhibitors (and ARBs) is hypotension (low BP), kidney failure and elevated potassium. These drugs, like all drugs, can cause what they are purported to 'protect'...

Blocking the final angiotensin at the receptor level is not good either. Recently angiotensin II receptor blockers (ARBs) are associated with a 20% relative increase in new cancer occurrence (7.2% v. 6.0%) compared with placebo in clinical trials (Sipahi et al, Lancet Oncology 2010). Lung cancer was the highest reported solid organ cancer incidence.

Food? Side effects? Generally not unless a food allergy exists to other food components or it promotes excessive insulin or blood glucoses or n-6/n-3 imbalances (e.g. starches, fruit, industrial farmed high n-6 meat/seafood).






Other Beneficial Foods Functioning as ACE-Inhibitors

Nutrigenomics is a new field that helps align our DNA expression to optimizing health via food, food components, and nutraceuticals (omega-3 fish oil supplements, vitamin D supplements, K2 supplements, magnesium, zinc, trace minerals, digestive enzymes, probiotics, etc). I discussed earlier: Nutrigenomics and Hypertension. The below list is adapted (I removed gluten #19).

Note: many of these are shore-based foods with high minerals (iodine, zinc, magnesium, selenium, manganese, chromium, etc).
1. Garlic
2. Seaweed
3. Tuna protein/muscle
4. Sardine protein/muscle (Anchovies too: Caeasar dressing)
5. Hawthorne berry
6. Bonito flakes (fish protein)
7. Pycnogenol (historical used flavonoid used as tea from pine bark)
8. Casein
9. Hydrolyzed Whey protein
10. Sour milk (fermented dairy)
11. Gelatin (protein)
12. Sake (fermented rice wine)
13. Omega-3 essential fatty acids -- even epigenetically reverses hypertension in bred rats
14. Chicken Egg Yolks
15. Zein (lysine and tryptophan-free protein from maize)
16. Dried Salted Fish
17. Fish sauce (fermented product)
18. Zinc
19. Rice bran (fatty acids, proteins)
20. Fermented cheeses
21. Tubers: potatoes, tumeric/curcumin, Japanese yams, Chinese yams,
22. Lactoferrin (human breastmilk, cow/goat/sheep dairy)
23. Cocoa storage protein
24. Pork protein/muscle
25. Chicken protein/muscle
26. Beef protein/muscle



Omega-3 Reverses Damage from Stressors (Insulin, Salt, Fructose, Cold Storage) and Epigenetically in Low-Protein-Mother and Stressed-Mother Rats

Omega-3 fish oil is just amazing stuff; it reduces ACE by more than one mechanism of action... It reverses all kinds of damage in rat studies and human studies caused by the S.A.D. and neolithic living. Unfortunately for the great majority of human trials, the research doses are often so low to be clinically inconsequential and inconclusive. For accurate results, I believe the dose needs to be calculated per person and based on (1) omega-3 deficiency and (2) accumulated omega-6 incorporation into cell membranes and adipose/fat stores. Current ratios in the U.S. of n-6/n-3 in blood or tissue membranes is 30:1 to (!!) 40+:1 and getting worse as we speak as many outspoken physicians, cardiologists and government agencies are trying to promote more high omega-6 canola oil and other oxidized refined vegetable oils to replace saturated fats.

Dietary n-3 PUFAs affect the blood pressure rise and cardiac impairments in a hyperinsulinemia rat model in vivo.
Rousseau D, Héliès-Toussaint C, Moreau D, Raederstorff D, Grynberg A.
Am J Physiol Heart Circ Physiol. 2003 Sep;285(3):H1294-302.

Interrelationships between salt and fish oil in stroke-prone spontaneously hypertensive rat.
Vaskonen T, Laakso J, Mervaala E, Sievi E, Karppanen H.
Blood Press. 1996 May;5(3):178-89.

Long-chain (n-3) polyunsaturated fatty acids prevent metabolic and vascular disorders in fructose-fed rats.
Robbez Masson V, Lucas A, Gueugneau AM, Macaire JP, Paul JL, Grynberg A, Rousseau D.
J Nutr. 2008 Oct;138(10):1915-22.

Beneficial effects of omega-3 fatty acid treatment on the recovery of cardiac function after cold storage of hyperlipidemic rats.
Ku K, Oku H, Kaneda T, Onoe M, Zhang Z.
Metabolism. 1999 Oct;48(10):1203-9.


Epigenetic implications:
Adult cardiorenal benefits from postnatal fish oil supplement in rat offspring of low-protein pregnancies.
Catta-Preta M, Oliveira DA, Mandarim-de-Lacerda CA, Aguila MB.
Life Sci. 2006 Dec 23;80(3):219-29.

Maternal fish oil supplementation benefits programmed offspring from rat dams fed low-protein diet.
Gregório BM, Souza-Mello V, Mandarim-de-Lacerda CA, Aguila MB.
Am J Obstet Gynecol. 2008 Jul;199(1):82.e1-7.

Developmental programming of renal glucocorticoid sensitivity and the renin-angiotensin system. [high omega-3 diet ameliorates high BP and high ACE activity in F1 generation born from rats given maternal-dexamethasone-dosing]
Wyrwoll CS, Mark PJ, Waddell BJ.
Hypertension. 2007 Sep;50(3):579-84. Free PDF.

The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11beta-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero.
Bertram C, Trowern AR, Copin N, Jackson AA, Whorwood CB.
Endocrinology. 2001 Jul;142(7):2841-53.


Human study:
Fish oil [1.8 g EPA+DHA] prevents the adrenal activation elicited by mental stress in healthy [lean, young] men.
Delarue J, Matzinger O, Binnert C, Schneiter P, Chioléro R, Tappy L.
Diabetes Metab. 2003 Jun;29(3):289-95. Free PDF.

12 comments:

stephen said...

I am not a numbers guy, but I do common sense very well.

First it is scientist’s job to defend his work. The fact Campbell says he has better things to do than answer criticism of his work is very telling.

Second, the fact he attacks Denise instead of Denise’s analysis of the China Study tells me, he has no good answers to Denise’s analysis of the China Study.

Well like I said you do not need to understand numbers to understand who won this argument.

Daniel said...

Thanks for your post. I agree with you that we need to reduce our stress, balance our omega 6 and 3 ratio, and keep our insulin low to be free from many metabolic diseases in the future.

Do you recommend limiting our chicken and pork intake? since even if these animals are pastured, most of them are feed with grains which raised their omega 6 content in their fat. Also, can a high dose of fish oil daily be bad for health after a certain level?

Mike said...

I'm going to start taking away the captopril of patients I see and writing 'scripts for grass fed meat. :)

Jake said...

"Carnivorous Neanderthals and Why Failure To Evolve?" is on your RSS feed but in not on your blog.

Dr. B G said...

stephen,

Campbell is transparent? Have you seen Richard Nikoley's comments directed toward him on the amazon.com pages for the China Study? Campbell is a tried and true arrogant turd...


Daniel,

Well -- industry meat will accumulate damages because as you mentioned they are higher in omega-6 due to grain feeding. Pastured and grassfed pork, chicken and beef apparently seem to have much lower n-6 and significantly higher n-3.

Cover bets with high quality fish oil supplements. With the Florida incidence, I think prices will sky rocket later...

Yes -- immunosuppression and affects on clotting factors may occur with supratherapeutic dosages of omega-3. I've only seen nose bleeds in those prone and in those in renal failure. Something about the kidneys affects platelet and clotting factor function...


Jake!

PATIENCE -- it's evolving *haaa ah!* D*MN -- sorry, I always press the publish 'button' by accident.

-G

Jake said...

Over a year ago I did most of the things you said to reduce my blood pressure.

At that time, my blood pressure was 140/90 without medication. With an ACE inhibitor, my blood pressure was 130/85.

Now my blood pressure is 118/70 and I am off of blood pressure medicine.

Thank you Dr. B G

Dr. B G said...

Jake,

You did it.

Ahhh AH... Congratulations! That's WONDERFUL. I can't wait to see awfully HAAAWWT body... of evidence for revolutionary and evolutionary health *winky*

-G

stephen said...

Jake

What did you do?

stephen said...

Now I am angry:

Campbell:

"Before proceeding further, however, I would like to make a general comment about my approach in responding to Denise. I believe Denise is a very intelligent person, and I can see how she might reach the conclusions she did; this is easy to do for someone without extensive scientific research experience. Having said this, there are fundamental flaws in her reasoning, and it is these flaws that I will address in this paper. Some might wonder, “Why didn’t he go through her laundry list of claims and address each one in the same order?” The answer is simple: these claims are derived from the same faulty reasoning, so it is this underlying problem that I will address. I do in fact illustrate this point by addressing one of her claims regarding wheat, and the reader can assume that one could go through a similar exercise with all her claims...

Denise makes a point concerning a highly significant (but unadjusted) univariate correlation between wheat flour consumption and two cardiovascular diseases plus a couple other diseases. In doing so, she infers that wheat flour causes these cardiovascular diseases. She also makes the point that “none of these correlations appear to be tangled with any risk-heightening variables, either.” And further, she implies that I ignored this potentially important correlation, perhaps intentionally, because of my alleged bias against meat. I use this particular example here because others who very much dislike my views have pointed out on the Internet that this example cited by Denise represents evidence of my lack of integrity...

Not only does Denise misrepresent and misunderstand the rationale for the science in The China Study, her choice of words do not facilitate what she hopes to achieve. Her overall message, often embellished with adjectives and subjective remarks, appeals to some questionable characters sympathetic to or subservient to the Weston A Price Foundation, a farm lobbying group whose advocates and apologists have accused me of being a “fraud”, a “liar”, a “buffoon” and (earlier) an associate of a “terrorist” organization. I doubt that this is what she wanted to achieve. These individuals, for much too long, have been carelessly using or even ignoring science to further their own interests, such as advocating for the use of a very high fat, high protein diet mostly consistent with the diet that has caused us so much difficulty."


The Whole Response here ===> http://campbellcoalition.com/?p=142

so now Denise Minger is writing a Response to Campbell's response.
http://rawfoodsos.com/2010/07/22/super-quick-china-study-update/

Wow again attacking Denise again instead of her analysis of the China Study.

Campbell do you have no shame?

stephen said...

like reading Dr. Harris' blog:

Below is from his Statins and the Cholesterol Hypothesis – Part I Posting:

"I do not believe in any of the versions of the lipid hypothesis, ranging from Ancel Keys' original idea that cholesterol or dietary fat clogs the arteries, to the currently fashionable one that “small, dense” LDL particles are like microscopic rodents that are designed to burrow under the intima of your blood vessels and kill you."

http://www.paleonu.com/panu-weblog/2010/7/21/statins-and-the-cholesterol-hypothesis-part-i.html

It is a interesting read and I wonder what you think about this post.

Especially the part he says the “small, dense LDL particles" don't hurt us.

Dr. B G said...

stephen,

Yes I read it earlier today and that is another epic, erudite (FUNNY) post from Dr. Harris.

Centenarian studies back it up -- sdLDL range 20-30+% of the total LDL and they are completely, totally healthy... physically and mentally. A CETP SNP was one variable in Ashkenazi Jewish however that is not replicable in our centenarian or long-living subpopulations it turns out! High trad'l schmaltz diet? Other genetic adaptive advantages that we do not recognize or understand yet?

However if one has already had disease of coronary or renal or cerebral or peripheral arteries or heart failure, then one has to figure out why that occurred in the first place. If disease occurred at a level where the sdLDL% was 10% -- well that 10% is probably a bit too high for that individual. The 90% of large buoyant LDL fraction are probably dysfunctional as well. In all the clinical trials in humans with chronic diseases that I've seen, when the sdLDL% decreases, many other biomarkers of health status improve as well with the intervention (e.g. exercise, diet, omega-3, vitamin D, etc).

Kurt knows how feel but I don't think EBCT or CAC assessments are necessary. NMR and BHL testing are additionaly superfluous (and d*mn f*ckin expensive all told) when diet, supplements, sleep and exercise are in line...

High blood pressure is another indicator of calcifications. If everything is working right, the BP should be normalizing over 6 to 24 months. If not, then something is absolutely not right. (e.g. statins -- statins s*ck; hormonal imbalances... s*ck too)

Sources of inflammation which lead to elevated sdLDL need to be identified, located then extinguished.

I agree with him as well that the best strategy is a evo/paleonu approach.

However value in supplemental approaches is something traditionally trained physicians fail to grasp and take advantage of. It is great that Harris and other evo/paleo docs are so open minded.

Indeed pharmaceuticals are actually all around us -- food, omega-3 fish oil, magnesium supplements, K2 drops -- call a rose by any other name...!

-G

Dr. B G said...

stephen,

Yes I read it earlier today and that is another epic, erudite (FUNNY) post from Dr. Harris.

Centenarian studies back it up -- sdLDL range 20-30+% of the total LDL and they are completely, totally healthy... physically and mentally. A CETP SNP was one variable in Ashkenazi Jewish however that is not replicable in our centenarian or long-living subpopulations it turns out! High trad'l schmaltz diet? Other genetic adaptive advantages that we do not recognize or understand yet?

However if one has already had disease of coronary or renal or cerebral or peripheral arteries or heart failure, then one has to figure out why that occurred in the first place. If disease occurred at a level where the sdLDL% was 10% -- well that 10% is probably a bit too high for that individual. The 90% of large buoyant LDL fraction are probably dysfunctional as well. In all the clinical trials in humans with chronic diseases that I've seen, when the sdLDL% decreases, many other biomarkers of health status improve as well with the intervention (e.g. exercise, diet, omega-3, vitamin D, etc).

Kurt knows how feel but I don't think EBCT or CAC assessments are necessary. NMR and BHL testing are additionaly superfluous (and d*mn f*ckin expensive all told) when diet, supplements, sleep and exercise are in line...

High blood pressure is another indicator of calcifications. If everything is working right, the BP should be normalizing over 6 to 24 months. If not, then something is absolutely not right. (e.g. statins -- statins s*ck; hormonal imbalances... s*ck too)

Sources of inflammation which lead to elevated sdLDL need to be identified, located then extinguished.

I agree with him as well that the best strategy is a evo/paleonu approach.

However value in supplemental approaches is something traditionally trained physicians fail to grasp and take advantage of. It is great that Harris and other evo/paleo docs are so open minded.

Indeed pharmaceuticals are actually all around us -- food, omega-3 fish oil, magnesium supplements, K2 drops -- call a rose by any other name...!

-G