Bring Back Brown Bag Breathing
Even though in more recent times it has been given a bad name, carbon dioxide, and its production (and retention) in the body, is part of a process which is involved with protection against stress, and disease.
Put another way, too much stress – or anything that interferes with thyroid energy system function – can hinder the ability of the body to produce carbon dioxide (CO2), eventually lowering overall metabolic performance. Stress promotes hyperventilation (or overbreathing), and hyperventilation also promotes stress, as well as the reduction in CO2 levels in the body, and interference with metabolism.
“…there is growing evidence regarding an association between subclinical hypothyroidism and atherosclerosis, coronary heart diseases, and hypertension…Hypothyroidism, particularly at the subclinical stage, results in hyperventilation as demonstrated by a low Et-CO2.” (Ansarin K, et al., 2011)
Excess stress and the continuous suppression of thyroid energy metabolism, has been scientifically demonstrated to promote many different kinds of disease, and part of the reason for this involves the important link between suppressed thyroid, hyperventilation, and low CO2 levels in the body. Also, as energy systems are interfered with, and as CO2 decreases, lactate production tends to rise, and increasing exposure to lactic acid is another factor involved with disease promotion.
“Sustained or spontaneous hyperventilation has been associated with a variety of physical symptoms and has been linked to a number of organic illnesses and mental disorders…Raising CO2 levels by means of therapeutic capnometry has proven beneficial…and the reversing of hyperventilation has emerged as a potent mediator for reductions in panic symptom severity and treatment success.” (Meuret AE, Ritz T, 2010)
“Severe sepsis and septic shock are responsible for significant morbidity and mortality among patients admitted to the emergency department…We…demonstrate an inverse relationship between exhaled Etco2 levels and serum lactate levels, and lower mean Etco2 levels in nonsurviving patients.” (Christopher L. Hunter, MD, PhD et al., 2013)
“Compared with otherwise similar patients residing at or near sea level, patients living at ≥ 6000 ft had 31%…lower rates of myocardial infarction, 27%…lower rates of stroke and 19%…lower rates of cardiovascular death.” (Winkelmayer WC, et al., 2012)
A well functioning metabolism uses sugar in the presence of oxygen, to efficiently produce energy and carbon dioxide. In fact, the presence of carbon dioxide alone, is known to be a good indicator of effective mitochondrial energy production.
When the by-products of excessive stress or thyroid dysfunction interfere with this process, cells begin to produce energy far less fruitfully, shifting towards a less efficient state, increasingly converting glucose to lactic acid (rather than carbon dioxide), relying more upon the oxidation of fat for energy, much of which (particularly these days) tends to be the polyunsaturated fatty acids (PUFAs).
Thyroid hormone avalability and functionality, is central to oxidative metabolism and the production of carbon dioxide, and the polyunsaturated fats (PUFAs) have been shown to interfere with thyroid hormone on many physiological levels.
“…profoundly lowered basal metabolic rate and decreased CO2 production, resulting probably from severe hypothyroidism, may have resulted in development of acute respiratory alkalosis…” (Lee HT, et al., 1999)
The hypothyroid hyperventilation state, promotes the release of the stress hormones adrenaline and cortisol, which further interfere with mitochondrial respiration, inhibiting thyroid function, shifting towards the oxidation of fat, decreasing CO2 and increasing lactic acid. Lactic acid itself interferes with metabolism and causes stress.
“…baseline fear scores correlated inversely with PCO2 levels and positively with cortisol levels while PCO2 levels correlated negatively with cortisol levels. Significant predictors of lactate-induced panic were prelactate infusion fear and the interaction of high cortisol levels and low PCO2 levels…synchronized elevations of HPA axis activity, self-reported fear, and hyperventilation…predisposes to lactate-induced panic.” (Coplan JD, et al., 1998)
“Several lines of evidence suggest that lactate metabolism may be altered in panic disorder… patients who panicked during hyperventilation exhibited larger increases in serum lactate levels than nonpanicking patients…Hyperventilation-induced panic appears to be associated with metabolic changes leading to elevated serum lactate…” (Maddock RJ, et al., 1991)
So although the production of lactate (an important factor involved in cancer growth and spread) can become chronically increased due to continuous metabolic interference, it is also something which can end up making a return to more optimal function – with effective glucose oxidation and carbon dioxide production – more difficult. Metabolic suppression, hyperventilation and low CO2 promotes hypoxia, which is central to cancer progression.
Stress – combined with inefficient metabolic function – promotes the absorption into circulation of bacterial endotoxin, further damaging respiration, and increasing the release of many stress related substances (such as serotonin, estrogen and nitric oxide), which can then cause more stress, inflammation and interference with energy metabolism.
Hyperventilation, low Co2, and rising levels of serotonin and nitric oxide have been shown to be factors involved in the worsening of asthma severity, and there is a relationship between asthma and mood disorders like depression or anxiety, also known to be conditions of stress and hypometabolism.
“Our finding that free serotonin was…closely associated with clinical severity and pulmonary function suggests that this factor plays an important role in the pathophysiology of acute asthma.” (Lechin F, et al., 1996)
“A high prevalence of anxiety, hyperventilation and depression exists amongst our severe asthmatics. Hyperventilation and anxiety were associated with uncontrolled asthma…” (Tan Li Leng karen, et al., 2015)
It’s probably no great surprise that it has also been shown that there is an increased risk of cancer amongst patients with severe asthma, not to mention the metabolic stress related connection between cancer, anxiety and depression. Increased CO2 (and decreased lactate) production is likely to be protective.
“Patients with multiple hospital admissions showed a high risk, particularly for stomach and colon cancers…The relatively stable temporal trends suggest that the asthmatic condition rather than its medication is responsible for the observed associations.” (Ji J, et al., 2009)
“Anxiety activates the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic-adrenal-medullary axis, elevating corticosterone and other stress hormones, such as catecholamines. These hormones could modulate the activity of the tumor microenvironment.” (Shen CC, et al., 2013)
The stress substances directly interfere with the oxidation of glucose, increasing lactic acid and helping to feed what can become a vicious cycle of degeneration and disease. The production of lactate increases in response to endotoxin, and lactate itself increases the inflammatory anti-metabolic effects of endotoxin.
“…bacterial infection and LPS increase lactate production, and lactate boosted LPS signaling-mediated inflammatory gene expression as shown by the present study…therefore…the actions of LPS and lactate lead to a vicious cycle that promotes TLR4-mediated inflammation and contributes to a number of diseases, including type 2 diabetes and cardiovascular disease.” (Samuvel DJ, et al., 2009)
“…LPS [endotoxin] does enter the circulation after ultra-endurance exercise and may, together with muscle damage, be responsible for the increased cytokine response and hence GI complaints in these athletes.” (Jeukendrup AE, et al., 2000)
So from a slightly different view, it can be understood that increasing carbon dioxide levels lowers lactic acid, leading to a reduction in stress hormone release, lower levels of polyunsaturated free fatty acids, less exposure to bacterial endotoxin, and an improvement in thyroid energy production. This then further increases the production of carbon dioxide, lowering stress even more.
Endotoxin exposure increases as a result of the things that promote stress, and when circulation of endotoxin rises, this directly causes inflammation and greater interference with metabolism, potentially resulting in life threatening sepsis.
“Low ETCO2 levels were the strongest predictor of sepsis, severe sepsis, and mortality among all prehospital variables…There were significant associations between prehospital ETCO2 and serum bicarbonate levels…and lactate…” (Hunter CL, et al., 2016)
Hypoventilation leading to increased CO2, has been shown to be an effective method of treatment for panic disorders as well as asthma, and it makes sense that it is a good approach to improving any condition which relates to stress and inflammation, which is basically every condition.
“Hyperventilation-induced hypocapnia is common among asthma patients…capnometry-assisted respiratory training…aimed at normalizing basal and acute levels of end-tidal carbon dioxide (PCO2)…basal levels of PCO2 increased from hypocapnic to normocapnic range over the course of treatment. Improvements were accompanied by improvements in lung function and reductions in diurnal lung function variability. Improvements remained stable throughout follow-up.” (Ashton M. Jeter, et al., 2012)
“…the induction of therapeutic hypercapnia by continual inhalation of carbon dioxide…improves respiratory function and mitigates…lung and systemic inflammation…the statistically significant reduction in the levels of local and systemic inflammation by therapeutic hypercapnia may benefit patients by speeding recovery and reducing potential complications in the clinic…” (Wei Gao, M.D. et al., 2015)
Insufficient intake of sugar and protein (and some other nutrients) interferes with the production of thyroid hormone, reducing CO2, moving things in the direction of stress and inflammation, and away from efficient oxidative energy production.
It seems as though the things that get a bad name today, including sugar, salt, CO2, saturated fats, cholesterol, testosterone and progesterone, are protective, and the things that can be the most harmful, like estrogen, serotonin, nitric oxide, lactic acid, PUFAs and iron, get a free pass. I wonder why?
High lactic acid in the blood is a basic sign of stress and chronic inflammation, and an indication that thyroid metabolism has been suppressed. Anything that helps to promote oxidative metabolism and reduce lactate levels, can be seen as being protective against stress and disease, and CO2 is a pro-metabolism, anti-stress, anti-inflammatory substance.
Chronic metabolic stress, thyroid dysfunction and inflammation, have all been shown to be related to the development of cancer, heart disease, diabetes, as well as conditions such as asthma, depression and anxiety. Improving metabolism and CO2 production, helps to lower lactic acid, estrogen, serotonin, nitric oxide, free fatty acids, and other inflammatory disease promoting things.
Stress and the increased release of the polyunsaturated free fatty acids, promotes hyperglycemia, and hyperglycemia increases lactic acid production. Lactic acid is an independent predictor of insulin resistance and diabetes. Measuring CO2 exhalation is powerfully diagnostic. Sugar helps to lower free fatty acids and lactate, increasing CO2, and as such, is an anti-diabetes substance.
“Acute complications of diabetes include severe hyperglycaemia, diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS)…ETCO2 [end tidal CO2] had a uniquely high diagnostic accuracy overall, and at ETCO2 cut-off of 24.5 mmHg; it was highly sensitive (90 %) and specific (90 %)…” (Bou Chebl R, et al., 2016)
Some of the dietary measures which have been explored in an attempt to achieve a pro-metabolic state, include the provision of sufficient protein and other nutrients (from milk and cheese and gelatinous meats), the limiting of difficult to digest starches and fibers (from grains, beans, nuts and under cooked vegetables), and plenty of carbohydrate from sources such as sweet ripe fruits and juices, honey and white sugar.
Chronic endurance exercise has been shown to interfere with active thyroid hormone (T3) function (as well as reducing Co2 levels), most likely at least partially as a result of excessive intake of oxygen or hyperventilation.
Both salt and sugar, can help to suppress the stress hormones and promote the production of carbon dioxide, increasing thyroid energy production in general, and they have been used as part of an approach, helping to protect against some of the damaging effects of excessive exercise or training, and other forms of stress.
Some other pro-metabolism, pro-CO2 anti-stress things include thiamine (B1), acetazolamide, methylene blue, aspirin, niacinamide, vitamin D, K, biotin and B6, coconut oil, red light, and cyproheptadine.
A couple of teaspoons of sodium bicarb spread over a day, has been shown to have many metabolically beneficial effects.
“…these data demonstrate that the ingestion of sodium bicarbonate in youth athletes is an effective buffer during high intensity interval swimming and suggest that such a procedure can be used in youth athletes to increase training intensity as well as swimming performance in competition…” (Zajac A, et al., 2009)
Regular daily bag breathing is a cheap and easy method which is used to help to increase carbon dioxide levels, lower lactic acid production, improve thyroid energy metabolism, and generally protect against stress, inflammation and disease. Adaptation to a high altitude promotes CO2 and lowers lactic acid, and has been shown to be highly disease protective.
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J Intern Med. 2008 Jan;263(1):70-8. Exhaled NO and iNOS expression in sputum cells of healthy, obese and OSA subjects. Depalo A, Carpagnano GE, Spanevello A, Sabato R, Cagnazzo MG, Gramiccioni C, Foschino-Barbaro MP.
Arch Gen Psychiatry. 1998 Feb;55(2):130-6. Plasma cortisol concentrations preceding lactate-induced panic. Psychological, biochemical, and physiological correlates. Coplan JD, Goetz R, Klein DF, Papp LA, Fyer AJ, Liebowitz MR, Davies SO, Gorman JM.
Ann Intensive Care. 2017 Dec;7(1):31. Acute hyperventilation increases the central venous-to-arterial PCO2 difference in stable septic shock patients. Mallat J, Mohammad U, Lemyze M, Meddour M, Jonard M, Pepy F, Gasan G, Barrailler S, Temime J, Vangrunderbeeck N, Tronchon L, Thevenin D.
PLoS One. 2013;8(1):e55113. Lactate and risk of incident diabetes in a case-cohort of the atherosclerosis risk in communities (ARIC) study. Juraschek SP, Shantha GP, Chu AY, Miller ER 3rd, Guallar E, Hoogeveen RC, Ballantyne CM, Brancati FL, Schmidt MI, Pankow JS, Young JH.
Cell. 2015 Apr 23;161(3):595-609. A lactate-induced response to hypoxia. Lee DC, Sohn HA, Park ZY, Oh S, Kang YK, Lee KM, Kang M, Jang YJ, Yang SJ, Hong YK, Noh H, Kim JA, Kim DJ, Bae KH, Kim DM, Chung SJ, Yoo HS, Yu DY, Park KC, Yeom YI.
Anesth Analg. 2017 Oct;125(4):1261-1266. Low End-Tidal Carbon Dioxide at the Onset of Emergent Trauma Surgery Is Associated With Nonsurvival: A Case Series. Dudaryk R, Bodzin DK, Ray JJ, Jabaley CS, McNeer RR, Epstein RH.
Am Rev Respir Dis. 1993 Aug;148(2):330-8. Role of hyperventilation in the pathogenesis of central sleep apneas in patients with congestive heart failure. Naughton M, Benard D, Tam A, Rutherford R, Bradley TD.
Neuro Endocrinol Lett. 2006 Feb-Apr;27(1-2):247-52. The effect of exhaustion exercise on thyroid hormones and testosterone levels of elite athletes receiving oral zinc. Kilic M, Baltaci AK, Gunay M, Gökbel H, Okudan N, Cicioglu I.
PLoS Biol. 2015 Jul 16;13(7):e1002202. Lactate Regulates Metabolic and Pro-inflammatory Circuits in Control of T Cell Migration and Effector Functions. Haas R, Smith J, Rocher-Ros V, Nadkarni S, Montero-Melendez T, D’Acquisto F, Bland EJ, Bombardieri M, Pitzalis C, Perretti M, Marelli-Berg FM, Mauro C.
Scand J Med Sci Sports. 2014 Feb;24(1):80-8. Inhibition of tryptophan hydroxylase abolishes fatigue induced by central tryptophan in exercising rats. Cordeiro LM, Guimarães JB, Wanner SP, La Guardia RB, Miranda RM, Marubayashi U, Soares DD.
Ann Physiol Anthropol. 1989 Apr;8(2):71-7. Effects of carbon dioxide inhalation prior to maximal exercise on blood lactate and physical performance. Miyamura M, Ishida K, Hiruta S, Mokushi K, Ohkuwa T, Kanao Y.
Turk Kardiyol Dern Ars. 2010 Dec;38(8):537-43. Turkish. [The effects of thyroid hormones and interleukin-8 levels on prognosis after congenital heart surgery]. Baysal A, Saşmazel A, Yıldırım Aİ, Koçak T, Sunar H, Zeybek R.
West J Emerg Med. 2013 Nov;14(6):590-4. Predictive value of capnography for suspected diabetic ketoacidosis in the emergency department. Soleimanpour H, Taghizadieh A, Niafar M, Rahmani F, Golzari SE, Esfanjani RM.
Medicine (Baltimore). 2017 Sep;96(35):e7881. Usefulness of end-tidal carbon dioxide as an indicator of dehydration in pediatric emergency departments: A retrospective observational study. Yang HW, Jeon W, Min YG, Lee JS.
Chest. 2012 Dec;142(6):1562-1568. Fraction of exhaled nitric oxide and bronchial responsiveness are associated and continuous traits in young children independent of asthma. Schoos AM, Chawes BLK, Bønnelykke K, Bisgaard H.
Neurosci Lett. 2001 Jul 27;308(1):25-8. Caffeine inhibits exercise-induced increase in tryptophan hydroxylase expression in dorsal and median raphe of Sprague-Dawley rats. Lim BV, Jang MH, Shin MC, Kim HB, Kim YJ, Kim YP, Chung JH, Kim H, Shin MS, Kim SS, Kim EH, Kim CJ.
Nat Commun. 2014 May 13;5:3775. Exercise training reduces resting heart rate via downregulation of the funny channel HCN4. D’Souza A, Bucchi A, Johnsen AB, Logantha SJ, Monfredi O, Yanni J, Prehar S, Hart G, Cartwright E, Wisloff U, Dobryznski H, DiFrancesco D, Morris GM, Boyett MR.
Acta Endocrinol (Copenh). 1987 Sep;116(1):102-7. The influence of free fatty acids on the free fraction of thyroid hormones in serum as estimated by ultrafiltration. Bregengård C, Kirkegaard C, Faber J, Poulsen S, Siersbaek-Nielsen K, Friis T.
PLoS One. 2012;7(11):e49189. Transcutaneous Application of Carbon Dioxide (CO2) Induces Mitochondrial Apoptosis in Human Malignant Fibrous Histiocytoma In Vivo. Onishi Y, Kawamoto T, Ueha T, Kishimoto K, Hara H, Fukase N, Toda M, Harada R, Minoda M, Sakai Y, Miwa M, Kurosaka M, Akisue T.
J Immunol. 2009 Feb 15;182(4):2476-84. Lactate Boosts TLR4 Signaling and NF-κB Pathway-Mediated Gene Transcription in Macrophages via Monocarboxylate Transporters and MD-2 Up-Regulation1. Samuvel DJ, Sundararaj KP, Nareika A, Lopes-Virella MF, Huang Y.
Carcinogenesis, Volume 38, Issue 2, 1 February 2017, Pages 119–133. Reexamining cancer metabolism: lactate production for carcinogenesis could be the purpose and explanation of the Warburg Effect. Iñigo San-Millán George A. Brooks.
Indian J Endocrinol Metab. 2016 Sep-Oct;20(5):674-678. Oxidative stress in hypothyroid patients and the role of antioxidant supplementation. Chakrabarti SK, Ghosh S, Banerjee S, Mukherjee S, Chowdhury S.
J Epidemiol Community Health. 2012 Jul;66(7):e17. Altitude, life expectancy and mortality from ischaemic heart disease, stroke, COPD and cancers: national population-based analysis of US counties. Ezzati M, Horwitz ME, Thomas DS, Friedman AB, Roach R, Clark T, Murray CJ, Honigman B.
Epilepsia. 2011 Jan;52(1):104-14. 5% CO2 is a potent, fast acting inhalation anticonvulsant. Tolner EA, Hochman DW, Hassinen P, Otáhal J, Gaily E, Haglund MM, Kubová H, Schuchmann S, Vanhatalo S, Kaila K.
Nephrology Dialysis Transplantation, Volume 24, Issue 3, March 2009. Exaggerated compensatory response to acute respiratory alkalosis in panic disorder is induced by increased lactic acid production. Yoshiyasu Ueda Masayo Aizawa Atsushi Takahashi Masamitsu Fujii Yoshitaka Isaka.
PLoS One. 2013;8(2):e57399. The Risk of Cancer in Patients with Generalized Anxiety Disorder: A Nationwide Population-Based Study. Shen CC, Hu YW, Hu LY, Hung MH, Su TP, Huang MW, Tsai CF, Ou SM, Yen SH, Tzeng CH, Chiou TJ, Chen TJ, Liu CJ.
Acta Physiol Scand. 1969 Sep-Oct;77(1):179-80. The Effect of Marked Hyperventilation upon Tissue Levels of NADH, Lactate, Pyruvate, Phosphocreatine, and Adenosine Phosphates of Rat Brain. Granholm L, Lukjanova L, Siesjö BK.
Int J Gen Med. 2011 Jan 7;4:29-33. End-tidal CO2 levels lower in subclinical and overt hypothyroidism than healthy controls; no relationship to thyroid function tests. Ansarin K, Niroomand B, Najafipour F, Aghamohammadzadeh N, Niafar M, Sharifi A, Shoja MM.
Oncol Rep. 2017 Jun;37(6):3688-3694. Optimization of antitumor treatment conditions for transcutaneous CO2 application: An in vivo study. Ueha T, Kawamoto T, Onishi Y, Harada R, Minoda M, Toda M, Hara H, Fukase N, Kurosaka M, Kuroda R, Akisue T, Sakai Y.
Radiother Oncol. 2002 Jan;62(1):77-85. Dynamics of tumor oxygenation and red blood cell flux in response to inspiratory hyperoxia combined with different levels of inspiratory hypercapnia. Thews O, Kelleher DK, Vaupel P.
Br J Radiol. 2000 Oct;73(874):1100-4. Gas exchange parameters in radiotherapy patients during breathing of 2%, 3.5% and 5% carbogen gas mixtures. Baddeley H, Brodrick PM, Taylor NJ, Abdelatti MO, Jordan LC, Vasudevan AS, Phillips H, Saunders MI, Hoskin PJ.
Br J Cancer. 2009 Feb 24;100(4):644-8. Carbogen breathing increases prostate cancer oxygenation: a translational MRI study in murine xenografts and humans. Alonzi R, Padhani AR, Maxwell RJ, Taylor NJ, Stirling JJ, Wilson JI, d’Arcy JA, Collins DJ, Saunders MI, Hoskin PJ.
Vojnosanit Pregl. 1996 Jul-Aug;53(4):261-74. Serbian. Carbon dioxide inhibits the generation of active forms of oxygen in human and animal cells and the significance of the phenomenon in biology and medicine. Boljevic S, Kogan AH, Gracev SV, Jelisejeva SV, Daniljak IG.
Neoplasia. 2006 Jun;8(6):477-87. Carbogen Breathing Differentially Enhances Blood Plasma Volume and 5-Fluorouracil Uptake in Two Murine Colon Tumor Models with a Distinct Vascular Structure. van Laarhoven HW, Gambarota G, Lok J, Lammens M, Kamm YL, Wagener T, Punt CJ, van der Kogel AJ, Heerschap A.
Prehosp Emerg Care. 2014 Apr-Jun;18(2):180-4. Utility of initial prehospital end-tidal carbon dioxide measurements to predict poor outcomes in adult asthmatic patients. Nagurka R, Bechmann S, Gluckman W, Scott SR, Compton S, Lamba S.
Int J Cancer. Author manuscript; available in PMC 2016 Apr 1. Monitoring Oxygen Levels in Orthotopic Human Glioma Xenograft Following Carbogen Inhalation and Chemotherapy by Implantable Resonator Based Oximetry. Hou H, Krishnamurthy Nemani V, Du G, Montano R, Song R, Gimi B, Swartz HM, Eastman A, Khan N.
Clin Sci (Lond). 2000 Jan;98(1):47-55. Relationship between gastro-intestinal complaints and endotoxaemia, cytokine release and the acute-phase reaction during and after a long-distance triathlon in highly trained men. Jeukendrup AE, Vet-Joop K, Sturk A, Stegen JH, Senden J, Saris WH, Wagenmakers AJ.
Radiother Oncol. 1993 May;27(2):123-30. Changes in the oxygenation of head and neck tumors during carbogen breathing. Martin L, Lartigau E, Weeger P, Lambin P, Le Ridant AM, Lusinchi A, Wibault P, Eschwege F, Luboinski B, Guichard M.
J Asthma. 2014 Oct;51(8):839-46. Hyperventilation in asthma: a validation study of the Nijmegen Questionnaire–NQ. Grammatopoulou EP, Skordilis EK, Georgoudis G, Haniotou A, Evangelodimou A, Fildissis G, Katsoulas T, Kalagiakos P.
Clin Transl Allergy. 2015; 5(Suppl 2): P7. Anxiety, depression and hyperventilation symptoms in treatment-resistant severe asthma. Tan Li Leng karen, Tay Chee Kiang, Yii Anthony, Chan Kwok Wai Adrian, Lapperre Therese Sophie, and Koh Mariko Siyue.
Radiother Oncol. 1999 Feb;50(2):167-71. Improvement in human tumour oxygenation with carbogen of varying carbon dioxide concentrations. Powell ME, Collingridge DR, Saunders MI, Hoskin PJ, Hill SA, Chaplin DJ.