Monday, July 23, 2012

HEART DISEASE


Is There A Role For Nutraceuticals In Heart Disease?


Heart disease falls  into several classes: Coronary disease is the most frequent [1], but valvular [2] is not far behind: who doesn’t have a relative or friend who had some heart valve replaced or bypass surgery?
Actually [2] is giving epidemiology statistics:
“…Aortic valve sclerosis (aortic valve thickening and calcification without pressure gradient) seem to affect about one fourth of adults over 65 years of age, while the aortic valve stenosis is present in 2–9% of general population over 65 years of age; an increased prevalence of both sclerosis and stenosis with aging (48% and 4% in those over 85 years) is observed…”
  1. labtestsonline ; “common heart diseases” ; 2011
  2. Cardiovascular Ultrasound ;”Epidemiology and cardiovascular risk factors of aortic stenosis” ; 2006
Nutraceuticals are foods or food supplements taken to treat or relieve a disease. This post will examine whether some nutraceuticals can help in the fight against heart disease, particularly the stenosis or narrowing of the valves. 
First some background: In aortic stenosis (AS), the heart’s aortic valve narrows, making the heart work harder, and can result in Congestive Heart Failure (CHF), syncope,or angina, which are chest pains due to the lack of blood supply. So these are serious issues.
The literature has designated AS  as a progressive calcification disease most commonly caused by age, although it can have other causes like rheumatic fever or a congenital malformation.[1]
  1. Journal Of American Cardiology ; “Progression of aortic stenosis in 394 patients: relation to changes in myocardial and mitral valve dysfunction.”


Annotated Sketch Of Heart (Wikipedia Commons)
Most Cardiologists will recommend surgery to replace the valve, and there are two types of surgeries available:
  • The classical way is”Open Heart” (OH) . Although obviously a serious surgery, it has now been performed for many years. Open Heart, is obviously fully invasive, but proven technique if the patient is fairly is robust. [1]
  • A more recent procedure is the Trancatheter Aortic Replacement or TAVR or TAVI .  TAVR is less invasive, but relatively new. In TAVR, a replacement valve is passed through a hole in the groin by a puncture of the femoral artery and advanced up to the ascending aorta of the patient. Usually the method is for more frail patients. You still have to qualify, since the the vascular system has to be sturdy enough, and the surgeon has to bring in and set up the new prosthetic valve through the twists and turns of the heart itself albeit to different standards than the Open Heart. For example, severe aortic aneurisms that have the aortic valve blown up like a balloon and relatively thin walls, often preclude TAVR [2]
  1. Cleveland Clinic ; “Aortic Valve Surgery” ; March 2012
  2. CardioBrief ; “Consensus Document Provides Roadmap To Uptake Of TAVI In US” ; Jan 2012

There are two kinds of circumstances when a pharmaceutical or nutraceutical treatment would be of interest:
  • When somebody is declared  a non-candidate both for the OH and TAVR procedures
  • When the cardiologist declares the AS is to small to be a worthy of surgery
 This is where this post comes in, and you should discuss it with your Doctor or other health provider. Do choose someone who can think out of the box!
There is no direct pharmacologic treatment for AS. Doctors will usually prescribe drugs to alleviate arrythmias that can occur or to decrease the blood pressure and cholesterol levels. [1]
But after examination of the possible causes and processes, some nutraceuticals might help slow down the progression.
Calcific Aortic Stenosis is been seen by many studies as the result of an inflammatory process [2,3,4]
But what is inflammation?
Beneficial  inflammation is the initial response of the body to harmful stimuli and is achieved by the increased movement of plasma and white blood cells  from the blood into the injured tissues.
But then, there is mitochondrial inflammation: Mitochondria are cellular organelles responsible for generating biochemical energy. That kind of inflammation result in mitochondrial dysfunction.
The inflammation process was outlined in an excellent article of LifeExtension [5]. 
Summarizing:   Under oxidative stress, the cell membranes leaks some mitochondria components which are mistaken by the body’s immune system as threats. The body’s response is inflammation to get rid of the intruder, which bare some commonality with some autoimmune diseases like multiple sclerosis.


Mitochondrion in Animal Cell (Wikipedia Commons)
Since  mitochondria is such a basic component of our bodies, its malfunction through inflammation  brings about all sorts of diseases: From cancer, type II diabetes, osteoporosis, to cardiovascular issues.[2,3,4]…
More details about inflammation can be found in the excellent expose of LifeExtension [5]
  1. MayoClinic ; “Aortic Valve Stenosis: Treatments and Drugs”; 2012
  2. “Studies Provide Strongest Evidence To Date For Causative Role of Inflammation in Heart Disease” http://cardiobrief.org/2012/03/15/studies-provide-strongest-evidence-to-date-for-causative-role-of-inflammation-in-heart-disease/
  3.  “Spectrum of Calcific Aortic Valve Disease Pathogenesis, Disease Progression, and Treatment Strategies” ; Rosario V. Freeman, MD, MS; Catherine M. Otto, MD http://circ.ahajournals.org/content/111/24/3316/T5.expansion.html
  4. “Aortic valve stenosis: an active atheroinflammatory process.” http://www.ncbi.nlm.nih.gov/pubmed/17885417
  5. Life Extension  ; Chronic Inflammation ; 2012
Many studies have shown that  inflammation and oxidation often go hand in hand [1-4],  
  1. “Oxidation, Inflammation, and Aortic Valve Calcification: Peroxide Paves An Osteogenic Path” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2559856
  2. Dysregulation of antioxidant mechanisms contributes to increased oxidative stress in calcific aortic valvular stenosis in humans”. http://content.onlinejacc.org/article.aspx?articleid=1139184
  3. Journal Of American Cardiology ; “http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2559856/
  4. New Horizon ; “Nutritional antioxidants and the modulation of inflammation: theory and practice.” ; 1994
It was therefore natural to look at antioxidants to fight it. And there are many studies that back up this approach.
Antioxidants:
CoenzymeQ10, Selenium are antioxidants of choice[ 1,2], but the list is much longer. Treatment with full spectrum vitamin E has been abandoned by many because of negative results of large scale studies [3], but still has some defenders [4,5]. The consensus on Resveratrol is that it might help, but more studies are needed (as usual..) [6]
  1. Coenzyme Q10 in patients with end-stage heart failure awaiting cardiac transplantation: a randomized, placebo-controlled study. http://www.ncbi.nlm.nih.gov/pubmed/15188947
  2. Selenium and CoenzymeQ10: Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation http://www.ncbi.nlm.nih.gov/pubmed/22626835
  3. JAMA  ;”Effects of Long-term Vitamin E Supplementation on Cardiovascular Events and Cancer”; HOPE Trials ; March 2005 http://jama.jamanetwork.com/article.aspx?articleid=200541
  4. Genes and Nutrition ; “ Multifaceted role of tocotrienols in cardioprotection supports their structure: function relation” ; Jan 2012 ; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250529
  5. Linus Pauling Institute, U. of Oregon ; “FATALLY FLAWED” CLINICAL TRIALS OF VITAMIN E” ; http://lpi.oregonstate.edu/ss08/vitamine.html
  6. Mayo Clinic ; “”Red wine and resveratrol: Good for your heart?”; March 2011
In addition to  oxidation brings about inflammation,  they combine to generate a tissue structure attractive to calcification.
Quoting [1] “…In addition , oxidation and inflammation bring about  Oxidized LDL  (“bad” Cholesterol) stimulates valvular fibroblasts [biostructures] to release matrix vesicles, a nidus [nest] for early calcification…”  
Let us also translate [2]‘s title in plain English :
“…Peroxide Paves An Osteogenic Path” : Peroxide  [a potent oxidant] provides an osteogenic  path [a path for the generation of bone like structures]. In broader terms, an oxidant is misleading your body into generating  bone where it should not, your aorta!
  1. Circulation ; “Spectrum of Calcific Aortic Valve Disease Pathogenesis, Disease Progression, and Treatment Strategies”
    http://circ.ahajournals.org/content/111/24/3316.full
  2. Journal of American Cardiology ; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2559856/Oxidation, “Inflammation, and Aortic Valve Calcification: Peroxide Paves An Osteogenic Path
So to attempt to slow down aortic calcification, you should discuss with your  health provider the strategy of   decreasing oxidation, inflammation, and turning off the steady flow of blood serum calcium.
Calcium come into your body make-up by eating your regular food or food supplements. Post menauposal women at risk of osteoporosis, have been and often still are advised to load up on calcium  through food supplements. As a matter of fact it is still a standard recommendation.
Quoting WebMD [1]
“…Calcium supplements are standard for treating and preventing osteoporosis..”
Turns out, Calcium supplementation could be be harmful to the heart: Many recent studies are surfacing to point toward Calcium as a building block for various heart conditions, including vascular calcification
  1. WebMD ; Calcium
  2. Livestrong ; “ WHAT CAUSES CALCIUM DEPOSITS AND CALCIFICATION? ”http://www.livestrong.com/article/259570-what-causes-calcium-deposits-and-calcification/
  3. Calcium supplements: Bad for the heart?  “….evidence that calcium supplements exacerbated vascular calcification and contributed to the very high cardiovascular mortality experienced by those patients…” http://heart.bmj.com/content/98/12/895.extract
  4.  Nutrients 2010, 2(5), 505-522; doi:10.3390/nu2050505 “ReviewIs Excess Calcium Harmful to Health?”;   “…findings from a meta-analysis of randomized controlled trials (currently published in abstract form only) revealed that the use of calcium supplements was associated with an ~30% increased risk of myocardial infarction….” http://www.mdpi.com/2072-6643/2/5/505/htm
  5. NutraIngredients ; “New analysis slams calcium supplements over heart problems”; 2011 http://www.nutraingredients.com/Research/New-analysis-slams-calcium-supplements-over-heart-problems
In a nutshell most everyone agrees that supplements are the issue, but one should not avoid calcium one’s daily food.
However that distinction has been blurred by the government mandated  and and food industry eager compliance to, food “fortification”.
Regular milk contain 30% of your daily calcium requirements it is usually booosted to 40% , Yoghurt soy milk have the same issue. Except that soy does not contain calcium in the field, but is also often boosted to 40%! [4]. This is not fortification, but outright supplementation.
 There cannot be a discussion on nutraceutical and heart disease without focusing on Vitamin D, Vitamin K and Heart Disease:
Vitamin D regulate the availability of Calcium and its absosorption into the blood through the intestine [1].
Quoting:
“…facilitate intestinal absorption of calcium, although it also stimulates absorption of phosphate and magnesium ions. In the absence of vitamin D, dietary calcium is not absorbed at all efficiently. Vitamin D stimulates the expression of a number of proteins involved in transporting calcium from the lumen of the intestine, across the epithelial cells and into blood…”
The direct action of vitamin D on the heart is not clear,though [2]
Vitamin K controls  where the calcium is going to take hold. On the bone, where it should, or on endothelial tissues, where it should not.
Quoting [2] :
“…The vitamin K-dependent matrix Gla-protein (MGP) plays a dominant role… it is generally accepted that MGP is a potent inhibitor of arterial calcification…”
Ref 3-7 concur.
Note that Vitamin D is a complex of K1, K2, and that K2 is the one involved in calcium control [2].
  1. Colorado state U. ;Vitamin D (Calcitriol) ; http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/otherendo/vitamind.html
  2. AmedNews ; “Vitamin D’s impact on cancer and heart health needs more research” ;                                      http://www.ama-assn.org/amednews/2012/01/09/hlsa0109.htm
  3. Thrombosis and Haematostasis ; “Matrix Gla-protein: the calcification inhibitor in need of vitamin K”; 2008  http://www.ncbi.nlm.nih.gov/pubmed/18841280
  4. “Vitamin K-dependent Calcium Binding Proteins in Aortic Valve Calcification” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC371395/ Quoting: “…These results suggest that calcific valvar disease may result in part from vitamin K-dependent processes…”
  5.  The role of vitamin K in soft-tissue calcification. http://www.ncbi.nlm.nih.gov/pubmed/22516724
  6.  WebMD ; Integrative Medicine and Wellness ; “Vitamin K – Keeping Calcium in Your Bones and Out of Your Blood Vessels” ; Joe Pizzorno, Jr., ND http://blogs.webmd.com/integrative-medicine-wellness/2007/11/vitamin-k-keeping-calcium-in-your-bones-and-out-of-your-blood-vessels.html
  7. WebMD ; Integrative Medicine and Wellness ; “Vitamin K2, but Not Vitamin K1, is Helpful for Bone Density” ; Joe Pizzorno, Jr., ND http://blogs.webmd.com/integrative-medicine-wellness/2008/10/vitamin-k2-but-not-vitamin-k1-is-helpful-for-bone-density.html
So Vitamin K better do it’s job, if you take Vitamin D!
Conclusions:
Talk to your (enlightened) Doctor about this strategy against Coronary Heart Disease in general and  and Valvular Heart Disease:
Antioxidant supplements: CoQ10, Selenium
Anti-inflammatory: Omega-3 Fish Oil
Anti-Calcification: Limit your Calcium intake to RDA, take Vitamin K 2
Notes: 
CoQ10, and vitamin K can “thicken” your blood and interfere with blood thinners like Warfarin or aspirin. So people on those medications, and many heart patients are,  who want to take these antioxidants will be advised by their MD to test for their  prothrombin time (PT) test. .
Selenium can be toxic at high doses
Vitamin E will cause blood pressure to rise
Taking nutraceutical is more serious than most people believe!
Get help from your health practitioner before embarking on nutraceuticals treatments!
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