Happy Happy Heart

You’d think with all the guidelines and advice being handed out about heart health, hearts would be getting stronger, healthier and happier. But no, in upside down world, you might have to think again.

Just take a look at some of the existing biological evidence, relating to cardiovascular health and disease in general, and what you’ll probably realize, is that nothing the ‘health experts’ tell you, is what it is, because everything they say, is what it isn’t. It’s more than just curious.

I’ve talked about ways that ‘evil cholesterol’ protects against coronary artery disease, and how so called ‘heart healthy PUFAs’ cause atherosclerosis. But there’s more to heart health than just good arteries, and the ability of the heart to pump properly is also crucial.

You can’t separate the function of individual organs, from overall metabolism performance. And so, if you want to know the truth about what is and isn’t good for heart function, focusing on ‘top down’ official heart recommendations, which often seem to ignore basic physiological or metabolic principles, isn’t always very helpful, to say the least.

What does make sense, however, is to start by looking at how metabolism functions from the bottom up, so that you can get an appreciation of what things support or interfere with the ability of the heart to function optimally.

Whenever there is increased demand placed upon the body (and more oxygen is being consumed), a well functioning heart, will beat faster, but it will also beat harder. This principle, sometimes referred to as the Staircase Effect, allows for more blood to be pumped per contraction.

Alternatively, a weak, failing heart is unable to relax fully between contractions, and in an attempt to pump more blood when required, beats faster and weaker, and often pumps less blood than can be pumped by a strong healthy heart, with less beats.

So what is it that makes a heart strong and healthy, or weak and stressed? Like with metabolic function as a whole, it basically comes down to thyroid function and energy production, and the things that help or interfere.

“Patients with baseline or new-onset abnormal thyroid function had a higher mortality than those with normal thyroid function, even after controlling for other known mortality predictors…Abnormal thyroid function in patients with symptomatic HF [heart failure] is associated with significantly increased risk for death…” (Judith E. Mitchell, et al., 2013)

We could begin a discussion about metabolism and heart health, by talking about the polyunsaturated fats (PUFAs), chronic systemic inflammation, digestive dysfunction, bacterial issues and infection, vitamin and mineral imbalances and nutritional deficiencies in general, or just the substances of stress, like nitric oxide, lactic acid, serotonin, cortisol, and estrogen.

It doesn’t really matter where you start, because all roads lead to Rome. But I’m going to begin by talking about the role sugar has to play, because when it comes to metabolic function, it probably doesn’t get more central than the interplay between energy production and stress.

“The heart has a high rate of ATP production and turnover…required to maintain its continuous mechanical work. Perturbations in ATP generating processes may therefore affect contractile function directly….results suggest that augmenting cardiac glucose utilization could represent a potential strategy to treat HF [heart failure]…” (Doenst T, et al., 2013)

Sugar is fundamental to energy production, and thyroid energy systems are a basic protection against effects of stress exposure. In order for the heart to function properly under stress, energy needs to be made available, and not all ways are equal. Over time, exposure to less than optimal energy provision methods, can change the structure and function of the heart.

When stress is high and sugar availability is interfered with, thyroid system function can be suppressed, causing the heart to get more easily tired, at a time when it needs to work harder than normal. To help deal with this, defensive stress processes are activated.

One of the first things that happens, is that fat is released out of storage (as free fatty acids) in an attempt to provide alternate energy supply. Today, these fats are often highly polyunsaturated in composition, and the byproducts of the PUFAs powerfully suppress thyroid performance and promote inflammation, damaging the heart.

“Increasingly, the hypothyroid state, and in particular a low triiodothyronine level, has been associated with a reduced cardiac performance and poor prognosis in HF, even in the presence of normal thyroid-stimulating hormone levels.” (Schmidt-Ott UM, Ascheim DD, 2006)

“More severe heart failure was associated with higher thyroid-stimulating hormone (TSH), higher free thyroxine (FT4), and lower total triiodothyronine (TT3) concentrations…subclinical hypothyroidism…and isolated low T3 levels are associated with poor prognosis.” (Lakshmi Kannan, et al., 2018)

“Inflammation and HF are strongly interconnected and mutually reinforce each other. This indicates the difficulty to counteract inflammation and HF once this chronic vicious circle has started and points out the need to control the inflammatory process at an early stage avoiding chronic inflammation and HF.” (Van Linthout S, Tschöpe C. 2017)

When heart cells are damaged by a lack of energy and increased exposure to the breakdown products of the PUFAs, sugar is one thing that is required for healthy cellular regeneration, and unfortunately sugar is prevented (by the free fatty acids) from being used by the cells.

Lack of sugar availability also promotes exposure to adrenaline (and other catecholamines) and cortisol, which further interfere with the use of sugar, encouraging exposure to PUFAs, preventing optimal heart function.

“In congestive heart failure…FA utilization is induced whereas the glucose utilization rate is suppressed…high level of plasma norepinephrine may account for the elevated plasma free FAs…which…causes the decrement in glucose oxidation…Suppression of FAO may represent a promising strategy to improve myocardial energy homeostasis.” (Diem H. Tran, and Zhao V. Wang, 2019)

“…findings indicate that serum cortisol levels were a complementary and incremental cardiac event risk predictor in…patients with chronic heart failure and…cardiac event prediction based on cortisol levels was influenced by oxidative stress.” (Yamaji M, et al., 2009)

As part of this worsening stress scenario, lactic acid is produced in greater quantity, and the high lactic acid stress metabolism is another factor involved in the suppression of thyroid system function, and the promotion of heart failure.

“Elevated levels of arterial lactate on admission were related to worse in-hospital mortality in patients with ADHF [acute decompensated heart failure]…the presence of high lactate…could help stratify the initial risk of early mortality.” (Tomoharu Kawase MD, et al., 2015)

“…in patients suffering from acute myocardial infarction, a blood lactate level of over or equal to 2.5 mmol/l…may be used as an adjunct in identifying patients with higher risk of short term death, even in the absence of apparent signs of cardiogenic shock and hypotension.” (Gjesdal G, et al., 2018)

“In patients with acute coronary syndrome, cardiogenic shock and/or cardiac arrest…hyperlactatemia…is associated with worse outcome…Serial lactate measurements or lactate clearance have been reported to be more reliable for risk stratification in acute cardiac patients and…repeated measurement of lactate is highly advisable…” (Lazzeri C, et al., 2015)

A stressed, hypothyroid, inflamed heart, producing lactic acid (due to excessive exposure to PUFAs and interference with carbon dioxide producing sugar metabolism), causes the heart to become increasingly fibrotic, which then further impedes the heart’s pumping ability.

Increasing thyroid function, thereby lowering lactic acid (and promoting CO2 production), can reverse fibrosis in the heart, allowing the muscle to regenerate, enabling improved function.

“Thyroid system is strictly interconnected with heart homeostasis, and recent studies highlighted its role in cardioprotection, in particular through the preservation of mitochondrial function and morphology, the antifibrotic and proangiogenetic effect and also to the potential induction of cell regeneration and growth.” (Pingitore A, et al., 2016)

Interference with thyroid energy production tends to go together with increasing estrogen exposure (for a variety of reasons), and estrogen also interferes with the ability of the heart to pump optimally.

Any time lack of sugar (and oxygen) availability, prevents the heart from fully relaxing between contractions, the heart can retain excess water and calcium, further promoting estrogen, and encouraging collagen production, which leads to more fibrosis and a worsening of function.

Stress, lack of sugar and greater exposure to the PUFAs, inhibits digestion and promotes bacterial growth and the circulation of endotoxin throughout the system. Endotoxin is directly inflammatory and has also been shown to interfere with proper heart function.

“…we provided further support to the role of gut microbiota as a factor potentially implicated in cardiovascular disease by demonstrating that circulating LPS is associated with MACE [major adverse cardiovascular events] in AF [atrial fibrillation] patients during a long‐term follow‐up.” (Pastori D, et al., 2017)

Low thyroid energy production inhibits the intestinal barrier and liver function, allowing more endotoxin and other inflammatory things to interfere with the ability of the heart to pump properly, which then further reduces all functions, including digestion and liver.

“There is increasing evidence to suggest that a ‘leaky’ bowel wall may lead to translocation of bacteria and/or endotoxin, which may be an important stimulus for inflammatory cytokine activation in CHF. Furthermore, decreased cardiac function can contribute to reduce bowel perfusion and thereby impair the function of the intestinal barrier, leading to a vicious circle…” (Andreas Krack, et al., 2005)

Endotoxin impedes thyroid energy production, and apart from promoting estrogen, endotoxin increases exposure to nitric oxide and serotonin, and both of these directly suppress thyroid energy production, and are associated with heart failure and inflammatory metabolic illness in general.

“Plasma serotonin levels were significantly elevated in decompensated HF [heart failure] patients compared with stable patients…Higher plasma serotonin levels were associated with worse HF symptoms…and the presence of systolic dysfunction…” (Selim AM, et al., 2017)

“Inducible nitric oxide synthase (iNOS) protein is expressed in cardiac myocytes of patients…with congestive heart failure (CHF)…data implicate iNOS in the maladaptative response to systolic overload…selective iNOS inhibition…might be effective for treatment…” (Zhang P, et al., 2007)

“…iNOS generates higher and more sustained levels of NO than ecNOS, and it appears likely that high local concentrations of NO in cardiac myocytes exert important pathophysiological effects.” (Guy A. Haywood, et al., 1996)

“…there is a correlation between chronic overexpression of iNOS [inducible nitric oxide] and cardiac enlargement, conduction defects, sudden cardiac death, and…heart failure…selective inhibition of elevated iNOS activity may represent a valuable strategy for treatment of a variety of human cardiovascular conditions.” (Imran N. Mungrue, et al., 2002)

The saturated fats protect against inflammation and limit the release of PUFAs out of storage, enabling sugar metabolism and thyroid energy production, reducing estrogen production.

Estrogen promotes the breakdown of the PUFAs, which then go on to make the effects of estrogen more powerful, creating a potentially heart damaging cocktail.

“Malondialdehyde (MDA), a marker of lipid peroxidation, was measured in the plasma of patients with congestive heart failure (CHF)…a significant correlation…was found…between the MDA values and the duration in years (chronicity) of the CHF state.” (Díaz-Vélez CR, et al., 1996)

“We sought to study the markers of lipid peroxidation…in patients with varying degrees of heart failure. There was a significant positive correlation between the clinical class of heart failure and LPO [lipid peroxides ], MDA [malondialdehyde], sTNF…[ tumor necrosis factor-alpha] levels.” (Keith M, et al., 1998)

“4-Hydroxy-2-nonenal (4-HNE), a reactive aldehyde, is generated from polyunsaturated fatty acids (PUFAs)…4-HNE directly depresses contractile function…modulates cell signaling pathways, and can contribute to many cardiovascular diseases, including atherosclerosis, myocardial ischemia-reperfusion injury, heart failure, and cardiomyopathy. ” (Mali VR, Palaniyandi SS., 2014)

Sugar helps promote the production of cholesterol, and cholesterol plays a crucial role in protection against inflammation and endotoxin, and against stress in general.

Cholesterol is also a basic building block, in combination with a properly functioning thyroid metabolism, for the production of the anti-estrogen steroid, progesterone, which is known to improve the ability of the heart to pump effectively.

Cholesterol protects the cells, including heart cells, and so the combination of sugar restriction, increased exposure to PUFAs (which are known to interfere with cholesterol production), and cholesterol lowering statin drugs, can attack the heart in a triangulated fashion.

Based on all of this, it makes sense that improving thyroid energy metabolism, in a manner which provides enough sugar and protein and other important nutrients, without placing unnecessary stress on the digestive system and the liver, is a good overall strategy.

I’m not a doctor, but it seems logical to me that, as much as possible, all elements of a heart supportive strategy, should work in the same direction, protecting against excessive stress, inflammation and bacterial overload, avoiding exposure to the energy production damaging polyunsaturated free fatty acids and other thyroid interfering substances. Sugar appears to be a crucial factor required for success.

“Proinflammatory cytokines…play a key role in the pathophysiology of chronic heart failure, driving both symptomatic presentation and disease progression…this proinflammatory state…may be sustained through a chronic release of enterically derived bacterial endotoxin….bacterial decontamination of the gut with concomitant decrease in lipopolysaccharide (LPS) has a positive outcome on heart disease patients.” (Charalambous BM, et al., 2007)

“Mitochondrial oxidative metabolism is a promising target for the treatment of heart failure. An effective strategy appears to be inhibition of fatty acid oxidation and increasing the coupling of glycolysis to glucose oxidation…Modulating energy metabolism has the potential to improve cardiac function by improving the efficiency with which the heart utilizes ATP. This could lessen the energetic deficiency in ATP that can occur as the heart fails.” (Natasha Fillmore, Gary D.Lopaschuk, 2013)

A diet avoiding the inflammatory PUFAs, and the thyroid suppressive and difficult to digest grains, beans and legumes (and too much under cooked vegetable matter and starches), and with plenty of easy to digest protein and sugar and other nutrients from dairy, gelatin, and sweet fruits, white sugar and honey, is one potentially useful approach.

Raw carrot salad and very well cooked mushrooms, as well as numerous other pro-metabolism, anti-endotoxin, anti-estrogen, and generally anti-inflammatory, thyroid energy supportive things, many mentioned in previous articles, are also likely to be protective.

See More Here

Journal of Cardiac Failure Aug 2010 Volume 16, Issue 8, Supplement, Pages S33–S34. Serotonin as a Marker in Decompensated Systolic Heart Failure Ahmed M. Selim, Ramesh Chandra, Nitasha Sarswat, Pradnya Velankar, Myrna Littlewort, Norma Christian, Catherine Galvin, Ronald Zolty

European Heart Journal, Volume 26, Issue 22, November 2005, Pages 2368–2374. The importance of the gastrointestinal system in the pathogenesis of heart failure. Andreas Krack, Rakesh Sharma Hans R. Figulla Stefan D. Anker

Free Radic Biol Med. 2015 May;82:137-46. Lipid peroxidation product 4-Hydroxy-trans-2-nonenal (HNE) causes protein synthesis in cardiac myocytes via activated mTORC1-P70S6K-RPS6 signaling. Calamaras TD, Lee C, Lan F, Ido Y, Siwik DA, Colucci WS.

Shock. 2007 Jul;28(1):15-23. Role of bacterial endotoxin in chronic heart failure: the gut of the matter. Charalambous BM, Stephens RC, Feavers IM, Montgomery HE.

Am Heart J. 1996 Jan;131(1):146-52. Increased malondialdehyde in peripheral blood of patients with congestive heart failure. Díaz-Vélez CR, García-Castiñeiras S, Mendoza-Ramos E, Hernández-López E

Circ Res. 2013 Aug 30;113(6):709-24. Cardiac metabolism in heart failure: implications beyond ATP production. Doenst T, Nguyen TD, Abel ED.

Biochim Biophys Acta. 2013 Apr;1833(4):857-65. Targeting mitochondrial oxidative metabolism as an approach to treat heart failure Fillmore N, Lopaschuk GD.

BMC Cardiovasc Disord. 2018 Jan 18;18(1):8. Blood lactate is a predictor of short-term mortality in patients with myocardial infarction complicated by heart failure but without cardiogenic shock Grunde Gjesdal, Oscar Ö. Braun, J. Gustav Smith, Fredrik Scherstén and Patrik Tydén

Circulation. 1996;93:1087–1094. Expression of Inducible Nitric Oxide Synthase in Human Heart Failure Guy A. Haywood, Philip S. Tsao, Heiko E. von der Leyen, Michael J. Mann, Philip J. Keeling, Pedro T. Trindade, Neil P. Lewis, Christopher D. Byrne, Peter R. Rickenbacher, Nanette H. Bishopric, John P. Cooke, William J. McKenna, and Michael B. Fowler

Circ Heart Fail. 2018 Dec;11(12). Thyroid Dysfunction in Heart Failure and Cardiovascular Outcomes Kannan L, Shaw PA, Morley MP, Brandimarto J, Fang JC, Sweitzer NK, Cappola TP, Cappola AR.

J Cardiol. 2015 Feb;65(2):164-70. Validation of lactate level as a predictor of early mortality in acute decompensated heart failure patients who entered intensive care unit. Kawase T, Toyofuku M, Higashihara T, Okubo Y, Takahashi L, Kagawa Y, Yamane K, Mito S, Tamekiyo H, Otsuka M, Okimoto T, Muraoka Y, Masaoka Y, Shiode N, Hayashi Y.

J Am Coll Cardiol. 1998 May;31(6):1352-6. Increased oxidative stress in patients with congestive heart failure. Keith M, Geranmayegan A, Sole MJ, Kurian R, Robinson A, Omran AS, Jeejeebhoy KN.

World J Cardiol. 2015 Aug 26;7(8):483-9. Clinical significance of lactate in acute cardiac patients. Lazzeri C, Valente S, Chiostri M, Gensini GF.

Free Radic Res. 2014 Mar;48(3):251-63. Regulation and therapeutic strategies of 4-hydroxy-2-nonenal metabolism in heart disease. Mali VR, Palaniyandi SS.

JACC Heart Fail. 2013 Feb;1(1):48-55. Thyroid Function in Heart Failure and Impact on Mortality Mitchell JE, Hellkamp AS, Mark DB, Anderson J, Johnson GW, Poole JE, Lee KL, Bardy GH.

J Clin Invest. 2002 Mar;109(6):735-43. Cardiomyocyte overexpression of iNOS in mice results in peroxynitrite generation, heart block, and sudden death Mungrue IN, Gros R, You X, Pirani A, Azad A, Csont T, Schulz R, Butany J, Stewart DJ, Husain M.

J Am Heart Assoc. 2017 Jun 5;6(6). pii: e005784. Gut‐Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet. Pastori D, Carnevale R, Nocella C, Novo M, Santulli M, Cammisotto V, Menichelli D, Pignatelli P, Violi F.

Curr Heart Fail Rep. 2006 Sep;3(3):114-9. Thyroid hormone and heart failure. Schmidt-Ott UM, Ascheim DD.

Heart Lung Circ. 2017 May;26(5):442-449. Plasma Serotonin in Heart Failure: Possible Marker and Potential Treatment Target. Selim AM, Sarswat N, Kelesidis I, Iqbal M, Chandra R, Zolty R.

Curr Atheroscler Rep. 2017 Jun;19(6):27. Role of Inflammation in Heart Failure. Shirazi LF, Bissett J, Romeo F, Mehta JL.

J Am Heart Assoc. 2019 Jun 18;8(12):e012673. Glucose Metabolism in Cardiac Hypertrophy and Heart Failure. Tran DH, Wang ZV

Curr Heart Fail Rep. 2017 Aug;14(4):251-265. Inflammation – Cause or Consequence of Heart Failure or Both? Van Linthout S, Tschöpe C.

Circ Heart Fail. 2009 Nov;2(6):608-15. Serum cortisol as a useful predictor of cardiac events in patients with chronic heart failure: the impact of oxidative stress. Yamaji M, Tsutamoto T, Kawahara C, Nishiyama K, Yamamoto T, Fujii M, Horie M.

Circ Res. 2007 Apr 13;100(7):1089-98. iNOS deficiency protects the heart from systolic overload induced ventricular hypertrophy and congestive heart failure Zhang P, Xu X, Hu X, van Deel ED, Zhu G, Chen Y.

Endocr Connect. 2019 May 1;8(5):R76-R90. The impact of thyroid hormone dysfunction on ischemic heart disease. von Hafe M, Neves JS, Vale C, Borges-Canha M, Leite-Moreira A.

Cardiovasc Res. 2012 Jan 1;93(1):24-32. High intake of saturated fat, but not polyunsaturated fat, improves survival in heart failure despite persistent mitochondrial defects. Galvao TF, Brown BH, Hecker PA, O’Connell KA, O’Shea KM, Sabbah HN, Rastogi S, Daneault C, Des Rosiers C, Stanley WC.

Am J Physiol Heart Circ Physiol. 2018 May 1;314(5):H1049-H1052. Hypothesis: role for ammonia neutralization in the prevention and reversal of heart failure. Bing OHL.

Heart Fail Rev. 2016 Jul;21(4):391-9. Cardioprotection and thyroid hormones. Pingitore A, Nicolini G, Kusmic C, Iervasi G, Grigolini P, Forini F.

Image: Unknown