Categories:

Heart Arrhythmia

Also see:
Protect the Mitochondria
Thyroid Status and Cardiovascular Disease
“Normal” TSH: Marker for Increased Risk of Fatal Coronary Heart Disease
The Cholesterol and Thyroid Connection
High Blood Pressure and Hypothyroidism
A Cure for Heart Disease
Hypothyroidism and A Shift in Death Patterns
High Estrogen and Heart Disease in Men
Unsaturated Fats and Heart Damage
Estrogen Dominance and Magnesium Deficiency
Aldosterone as an endogenous cardiovascular toxin
Aldosterone and Thrombosis
Sodium Deficiency and Stress
Low Sodium Diet: High FFA, Insulin Resistance, Atherosclerosis
Sodium and Mortality: An Inverse Relationship
Ray Peat, PhD Quotes on Coconut Oil
Thyroid Hormones: The Ultimate Weapon Against Heart Disease?

All italic quotes by Ray Peat, PhD.

“Progesterone increases the heart’s pumping efficiency, and estrogen is antagonistic, and can produce cardiac arrhythmia.”

“Progesterone, which helps to maintain blood volume (partly by preventing vascular leakiness, preventing excessive sodium loss and by supporting albumin synthesis) antagonizes aldosterone. Aldosterone antagonists are now being recognized as effective treatments for hypertension, water retention, congestive heart failure, arrhythmia, diabetes, kidney disease, and a great variety of inflammatory problems.”

“Vitamins D and K, and calcium are important for stabilizing the heart rhythm. Estrogen tends to cause chemical hyperventilation (loss of carbon dioxide), which increases blood viscosity and the tendency toward atrial fibrillation. Progesterone and those other steroids have opposite effects (progesterone is a natural aldosterone antagonist, too). Thyroid is essential for helping cells to retain magnesium. A quart or two of milk, and a glass or two of orange juice every day helps with the main stabilizing minerals, but it’s good to have sea food once a week, especially shell fish, for the trace minerals.”

“A complete list of protective nutritional chemicals and natural drugs or analogs to our endogenous protective factors would be very long, but we should give special thought to certain ones, including succinic acid, which stimulates respiration and protective steroid synthesis; thyroid and vitamin E, which promote normal oxidation while preventing abnormal oxidation; magnesium; sodium and lithium, which help us to retain magnesium; tropical fruits, which contain GHB; coconut oil, which protects against cardiac necrosis, lipid peroxidation, hypothyroidism, hypoglycemia, and histamine damage; valium agonists, natural antihistamines; adenosine and uridine. Visits to higher elevations, and exposure’ to bright, long-wave light, can cause the body to optimize its own anti-stress chemistry. Avoiding the sense of being trapped is a high-level adaptive factor.”

Low DHEA:
“Albert Szent-Györgyi showed that the heart responds to progesterone, and more recently other researchers have presented evidence that DHEA is our “endogenous digitalis.”

Eur J Prev Cardiol. 2012 Nov 14. [Epub ahead of print]
Dehydroepiandrosterone sulfate levels and risk of atrial fibrillation: The Rotterdam Study.
Krijthe BP, de Jong FH, Hofman A, Franco OH, Witteman JC, Stricker BH, Heeringa J.
Background: High plasma dehydroepiandrosterone sulfate (DHEAS) levels have been associated with a reduced risk of cardiovascular disease and atherosclerosis. To our knowledge, no previous follow-up study has investigated the association between DHEAS and the development of atrial fibrillation. Our objective was to investigate the association between DHEAS levels and incident atrial fibrillation.Methods and results: The study was based on a random sample within the prospective population-based Rotterdam Study. The study population comprised 1180 participants without atrial fibrillation at baseline for whom baseline levels of DHEAS were measured in plasma. Atrial fibrillation was ascertained from centre visit electrocardiogram (ECG) assessments as well as medical records. During a mean follow-up period of 12.3 years, 129 participants developed atrial fibrillation. DHEAS levels were inversely associated with the risk of atrial fibrillation (hazard ratio (HR) per standard deviation (SD): 0.74, 95% confidence interval (CI): 0.58-0.94). Subjects in the highest DHEAS quartile had an almost three times lower risk of atrial fibrillation during follow-up, compared to those in the lowest DHEAS quartile (HR: 0.34, 95% CI: 0.18-0.64) adjusted for age, sex and cardiovascular risk factors.Conclusion: DHEAS can be regarded as an important indicator of future atrial fibrillation in both men and women, independent of known cardiovascular risk factors.

Exp Gerontol. 2002 May;37(5):701-12.
Dehydroepiandrosterone-sulfate serum levels and common age-related diseases: results from a cross-sectional Italian study of a general elderly population.
Ravaglia G, Forti P, Maioli F, Sacchetti L, Nativio V, Scali CR, Mariani E,
Zanardi V, Stefanini A, Macini PL.
The association of low serum dehydroepiandrosterone sulfate (DHEAS) levels with age, lifestyle, general health status indicators, and specific diseases was investigated in 436 men and 544 women of 65-97 yr old. In both sexes low serum DHEAS levels were associated with age, alcohol intake, number of current medications, and decreased thyroid function. Low DHEAS was also associated with low serum albumin in men and low systolic blood pressure in women. Compared to healthy men (n=106) age-adjusted serum DHEAS levels were significantly lower in men with atrial fibrillation, chronic obstructive lung disease, dementia, parkinsonism, cancer, diabetes, hypothyroidism, and in institutionalized men. Compared to healthy women (n=100) age-adjusted serum DHEAS levels were significantly lower in women with occlusive arterial disease, chronic obstructive lung disease, and osteoporosis. After controlling for differences in lifestyle and general health status parameters, low DHEAS levels remained statistically associated only with atrial fibrillation in men and osteoporosis in women, and it cannot be excluded that these association were spurious, due to multiple comparisons. These data suggest that in elderly people low serum DHEAS levels are more a non-specific indicator of aging and health status than a risk indicator of specific diseases.

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“Pregnenolone, progesterone, DHEA, testosterone, and thyroid all improve the stability of the heart.”

Reduced testosterone:
J Cardiovasc Electrophysiol. 2009 Sep;20(9):1055-60.
Deficiency of testosterone associates with the substrate of atrial fibrillation in the rat model.
Tsuneda T, Yamashita T, Kato T, Sekiguchi A, Sagara K, Sawada H, Aizawa T, Fu LT, Fujiki A, Inoue H.
BACKGROUND:
Since the prevalence of atrial fibrillation (AF) increases progressively with aging, especially in men, we hypothesized that testosterone might affect the occurrence of AF.
METHODS AND RESULTS:
We examined the electrophysiological properties of the atria in isolated-perfused hearts of sham-operated male (SM), female (SF), orchiectomized male with and without administration of testosterone (ORCH-T and ORCH), and ovariectomized female (OVX) Sprague-Dawley rats. An electrophysiological study revealed that repetitive atrial responses induced by electrical stimuli significantly increased in ORCH rats without changes in other electrophysiological properties and were abolished by administration of testosterone. To investigate the underlying mechanisms, we evaluated the expression level of calcium-handling proteins. In ORCH rats, the immunoreactive protein level of ryanodine receptor type 2 (RyR2) and sodium-calcium exchanger significantly increased as compared with SM and ORCH-T rats without alterations in the level of FK506-binding protein (FKBP12.6), sarcoendoplasmic reticulum Ca-ATPase, and phospholamban. Immunoprecipitation analysis demonstrated decreased binding of FKBP12.6 to RyR2 in ORCH rats, which was prevented by testosterone. In contrast, the expression levels of these proteins showed no significant differences between SF and OVX rats.
CONCLUSION:
Deficiency of testosterone was arrhythmogenic in rat atria possibly through less binding of FKBP12.6 to RyR2, which could induce feasible calcium leakage from the sarcoendoplasmic reticulum. These results would explain, at least in part, the increase in the prevalence of AF in accordance with the decline of testosterone particularly in elderly men.

Clin Cardiol. 2009 Jan;32(1):43-6.
Reduced testosterone levels in males with lone atrial fibrillation.
Lai J, Zhou D, Xia S, Shang Y, Want L, Zheng L, Zhu J.
BACKGROUND:
Sex hormones play an important role in the development of cardiovascular disease. Testosterone and estradiol have been reported to be down-regulated in subjects with coronary artery disease and heart failure, but has not been studied in atrial fibrillation (AF).
HYPOTHESIS:
Levels of sex hormones may be associated with susceptibility to lone AF in men.
METHODS:
Fifty-eight male subjects who had electrocardiographic evidence of paroxysmal or chronic AF and a structurally normal heart on echocardiography were enrolled. Subjects were excluded if they had been taking angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), or statins within 3 mo or had a history of coronary artery disease, rheumatic heart disease, cardiomyopathy, significant valvular disease, hyperthyroidism, or hypertension. Fifty-eight controls were recruited from a healthy outpatient population. Serum total testosterone and estradiol levels were determined using a commercially available radioimmunoassay.
RESULTS:
Mean levels of testosterone were significantly lower in subjects with lone AF when compared with controls (476 ng/dl versus 514 ng/dl, p = 0.005). No significant differences were found in the estradiol levels between the 2 groups (31.9 pg/ml versus 32.4 pg/ml, p = 0.789).
CONCLUSION:
Reduced testosterone levels may be associated with susceptibility to lone AF in men.

Med Hypotheses. 2010 Aug;75(2):269-70.
Testosterone as an atrial fibrillation treatment and stroke preventative in aging
men: case histories and hypothesis.

Eby G.

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Hypothyroidism:

“Broda Barnes showed that hypothyroidism causes heart disease, and also causes a tendency toward hypoglycemia. Low thyroid people compensate for the deficiency of energy and glucose (and of oxygen, for reasons similar to those mentioned above) by secreting an excess of adrenalin. Their 24 hour urine metabolites of adrenalin sometimes are 30 or 40 times normal. Recent studies that show that a moderate dose of thyroxin lowers lipid peroxidation confirm that thyroid has an antistress effect. The “conduction block” which occurs in hypothyroidism seems to be the same as the conduction block which develops in stress and predisposes to fibrillation.”

Neth Heart J. 2008 Feb;16(2):57-9.
Hypothyroidism as the cause of atrioventricular block in an elderly patient.
Schoenmakers N, de Graaff WE, Peters RH.
Department of Cardiology, Department of Internal Medicine, Tergooi Hospital
Blaricum, the Netherlands.
Syncope is a common problem in the older patient. Sometimes syncope is caused by
extreme bradycardia secondary to atrioventricular (AV) block. We describe a case
in which a 90-year-old woman presented with complete AV block due to severe
hypothyroidism. After suppletion with levothyroxine, AV conduction was restored.

(Neth Heart J 2008;16:57-9.).

Am J Med. 1990 Jun;88(6):638-41.
Recognition and management of cardiovascular disease related to thyroid dysfunction.
Ladenson PW.
Hypothyroidism and hyperthyroidism are both associated with clinically significant cardiovascular derangements. In hypothyroidism, these include pericardial effusion, heart failure, and the complex interrelationship between hypothyroidism and ischemic heart disease. Cardiovascular disorders associated with hyperthyroidism include atrial tachyarrhythmias, mitral valve dysfunction, and heart failure. Although these usually occur in individuals with intrinsic heart disease, thyroid dysfunction alone rarely causes serious but reversible cardiovascular dysfunction. Patients with commonly encountered cardiac disorders, e.g., idiopathic cardiomyopathy and atrial fibrillation, should be screened for potentially contributing subclinical thyroid diseases. In patients with heart failure and hypothyroidism, initial management should focus on diagnosis and optimal management of any primary cardiac disease, whereas in hyperthyroidism, aggressive measures to control excess thyroid hormone action should generally have the highest priority.

Recent Prog Horm Res. 2004;59:31-50.
Effects of thyroid hormone on the cardiovascular system.
Fazio S, Palmieri EA, Lombardi G, Biondi B.
Increased or reduced action of thyroid hormone on certain molecular pathways in the heart and vasculature causes relevant cardiovascular derangements. It is well established that overt hyperthyroidism induces a hyperdynamic cardiovascular state (high cardiac output with low systemic vascular resistance), which is associated with a faster heart rate, enhanced left ventricular (LV) systolic and diastolic function, and increased prevalence of supraventricular tachyarrhythmias – namely, atrial fibrillation – whereas overt hypothyroidism is characterized by the opposite changes. However, whether changes in cardiac performance associated with overt thyroid dysfunction are due mainly to alterations of myocardial contractility or to loading conditions remains unclear. Extensive evidence indicates that the cardiovascular system responds to the minimal but persistent changes in circulating thyroid hormone levels, which are typical of individuals with subclinical thyroid dysfunction. Subclinical hyperthyroidism is associated with increased heart rate, atrial arrhythmias, increased LV mass, impaired ventricular relaxation, reduced exercise performance, and increased risk of cardiovascular mortality. Subclinical hypothyroidism is associated with impaired LV diastolic function and subtle systolic dysfunction and an enhanced risk for atherosclerosis and myocardial infarction. Because all cardiovascular abnormalities are reversed by restoration of euthyroidism (“subclinical hypothyroidism”) or blunted by beta-blockade and L-thyroxine (L-T4) dose tailoring (“subclinical hyperthyroidism”), timely treatment is advisable in an attempt to avoid adverse cardiovascular effects. Interestingly, some data indicate that patients with acute and chronic cardiovascular disorders and those undergoing cardiac surgery may have altered peripheral thyroid hormone metabolism that, in turn, may contribute to altered cardiac function. Preliminary clinical investigations suggest that administration of thyroid hormone or its analogue 3,5-diiodothyropropionic acid greatly benefits these patients, highlighting the potential role of thyroid hormone treatment in patients with acute and chronic cardiovascular disease.

Pol Arch Med Wewn. 1983 Sep;70(3):81-5.
[Functional disorders of the heart conduction system as a symptom of thyroid hormone deficiency].
[Article in Polish]
Jonderko G, Kocot E, Marcisz C.

Nouv Presse Med. 1975 Jun 21;4(25):1859-62.
[Disorders of intra-cardiac conduction and hypothyroidism in adults. A systematic
study of 42 cases].

[Article in French]
Lardoux H, Cénac A, Perlemuter L, Bernheim R, Hazard J.
The rate of occurrence of disturbances of intracardiac conduction in association with adult hypothyroidism is not well known. On the basis of routine study of the electrocardiograms of 42 non-treated patients, disturbances of conduction were found in almost one third. Left anterior hemiblock (6/42) and first degree atrioventricular block (5/42) are the commonest. Bifascicular involvement is rare. Neither a trifascicular lesion nor complete AV dissociation were seen. There was no evident effect of hormone therapy on conduction disturbances. Their prognosis is good but they should perhaps be taken into consideration when the indications for beta-blockers are weighed.

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Magnesium retention compromised in hypothyroidism.

“Simply eating an adequate amount of calcium and magnesium can alleviate many problems related to stress and aging that are considered serious, such as heart arrhythmia, pancreatitis, and tissue calcification.”

“In hypothyroidism, the brain exciting hormones adrenaline, estrogen, and cortisol are usually elevated, and the nerve-muscle relaxant magnesium is low.”

“Low-thyroid cells are unable to retain magnesium efficiently, and a magnesium deficiency prevents muscle relaxation, wasting energy. Adequate sodium prevents urinary magnesium loss.”

“Magnesium, retained in the cell largely under the influence of ATP and thyroid, is our basic “calcium blocker,” or calcium antagonist.”

“Magnesium, which is protective against excitatory damage and is a calcium antagonist, tends to be retained in proportion to the activity of thyroid hormone.”

Am J Vet Res. 1978 Jan;39(1):159-61.
Effect of thyroid state on magnesium concentration of rat tissues.
Oliver JW.
The effect of alteration of thyroid status by thiouracil (0.1% concentration in drinking water for 60 days) or exogenous thyroxine (25 mg/dg of body weight administered SC from days 30 to 60) on magnesium content of rat tissues following exogenous magnesium was evaluated. Treatment of rats with magnesium solution (25 mg of magnesium sulfate/dg of body weight) resulted in increased magnesium concentration in most tissues of hypothyroid and hyperthyroid rats, with the mesenchymal-derived tissues (aorta, trachea, and ear cartilage) exhibiting the greatest increases (respectively, 154, 130, and 133% of control group values for hypothyroid rats, and 115, 108, and 107% of control group values for the hyperthyroid group). Magnesium concentration in skeletal and cardiac muscle was similar for hyperthyroid and control rats, but magnesium concentration in these same tissues of hypothyroid rats was decreased. Magnesium distribution and retention in rat tissues is altered considerably, depending on the functional status of thyroid gland.

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Consequences of magnesium deficiency on the heart.

Int J Biochem Cell Biol. 1997 Nov;29(11):1273-8.
Magnesium deficiency enhances oxidative stress and collagen synthesis in vivo in the aorta of rats.
Shivakumar K, Kumar BP.
Magnesium deficiency has been shown to produce vascular lesions in experimental animals, but the underlying mechanisms of vascular injury are not clear. It has been reported that in rodents, magnesium deficiency enhances circulating levels of factors that promote free radical generation and are mitogenic. In pursuance of these observations, the present study tested the hypothesis that magnesium deficiency may enhance oxidative stress and trigger an accelerated growth response in vivo in the aorta of rats. Oxidative stress was evaluated in terms of levels of thiobarbituric acid-reactive substances in the serum and aorta and activity of superoxide dismutase and catalase in the aorta; fractional rates of collagen synthesis were assessed using [3H]-proline. Serum and tissue levels of magnesium and calcium were determined by atomic absorption spectrophotometry. The present study demonstrated for the first time that magnesium deficiency significantly (P < 0.001) increases levels of thiobarbituric acid-reactive substances in the aorta of rats. Other changes in the aorta of animals on the Mg-deficient diet included a significant reduction (54%, P < 0.001) in the activity of superoxide dismutase and catalase (37%, P < 0.01) and a 19% increase in net fractional rates of collagen synthesis (P < 0.05). While serum magnesium was significantly reduced in these animals (P < 0.001), aortic tissue levels of magnesium in these animals remained unaltered throughout the duration of the study, suggesting the existence of other control mechanisms, apart from reduced tissue levels of magnesium, mediating the observed effects. These findings suggest that magnesium deficiency may trigger a wound healing response, involving oxidative injury and growth stimulation, in the vascular system.

Int J Biochem Cell Biol. 1997 Jan;29(1):129-34.
Magnesium deficiency-related changes in lipid peroxidation and collagen metabolism in vivo in rat heart.
Kumar BP, Shivakumar K, Kartha CC.
Magnesium deficiency is known to produce a cardiomyopathy, characterised by myocardial necrosis and fibrosis. As part of the ongoing investigations in this laboratory to establish the biochemical correlates of these histological changes, the present study probed the extent of lipid peroxidation and alterations in collagen metabolism in the heart in rats fed a magnesium-deficient diet for 28, 60 or 80 days. While lipid peroxidation was measured by the thiobarbituric acid reaction, collagen turnover rates and fibroblast proliferation were assessed using [3H]-proline and [3H]-thymidine, respectively. Tissue levels of magnesium and calcium were determined by atomic absorption spectrophotometry. A 39% increase in the cardiac tissue level of thiobarbituric acid reactive substances was observed on day 60 of deficiency (p < 0.001). A marked drop in collagen deposition rate (59%, p < 0.001%) on day 28 but a significant rise in fractional synthesis rate (12%, p < 0.001) and collagen deposition rate (24%, p < 0.001) on day 60 were observed. A fibroproliferative response in the heart was evident on day 80 but not at earlier time-points. Thus, the present study provides evidence of increased lipid peroxidation and net deposition of collagen in the myocardium in response to dietary deficiency of magnesium. These changes were, however, not directly related to alterations in the tissue levels of Mg. It is suggested that the increase in cardiac collagen synthesis and fibroplasia associated with Mg deficiency may represent reparative fibrogenesis, upon oxidative damage to the cardiac muscle, and is mediated by a mechanism independent of changes in cardiac tissue levels of Mg.

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Serotonin and heart arrhythmia:

Res Commun Chem Pathol Pharmacol. 1990 Jun;68(3):383-6.
5-Hydroxytryptamine (serotonin) enhances ventricular arrhythmias induced by acute
coronary artery ligation in rats.

el-Mahdy SA.
Ventricular arrhythmias were induced by acute coronary artery ligation in anesthetized rats. 5-Hydroxytryptamine (5-HT) in doses of 100-200 micrograms kg-1, given i.v. 5 minutes before coronary artery ligation, enhanced the severity of ventricular arrhythmias as shown by a significant dose-dependent increase in the number of ventricular ectopic beats, duration of ventricular tachycardia (VT) and ventricular fibrillation (VF). This effect was antagonized by pretreatment with the selective 5-HT2-receptor antagonist ritanserin (1 mg kg-1, i.p.) given 15 minutes before 5-HT. Ritanserin when used alone was observed to produce a significant reduction in the number of ventricular ectopic beats and duration of VT and VF. 5-HT significantly lowered the heart rate and produced initial rise of the systolic blood pressure (SBP). These effects were antagonized by ritanserin. Ritanserin significantly lowered the heart rate but did not alter the SBP. It was postulated that 5-HT might be implicated in the genesis and determination of severity of ventricular arrhythmias induced by acute myocardial ischemia, and that this effect is mediated via 5-HT2-receptors. 5-HT2-receptor antagonists may provide potential useful therapeutic agents for the management of these arrhythmias.

J Cardiovasc Electrophysiol. 2003 Feb;14(2):209-14.
5-hydroxytryptamine and atrial fibrillation: how significant is this piece in the puzzle?
Yusuf S, Al-Saady N, Camm AJ.
5-Hydroxytryptamine, a recent addition to the list of hormonal triggers for atrial fibrillation (AF), may play a pivotal role in the induction of AF related not only to cardiac surgery but also to acute coronary syndromes, valvular heart disease, cardiomyopathies, alcoholism, aging, and conducting tissue disease. This review examines the supporting laboratory and clinical evidence and provides a comprehensive insight into the basic underlying mechanisms involved. It also delves into the potential benefits and limitations of 5-HT4 antagonists in the prevention and management of this arrhythmia.

Psychosomatics. 2006 Nov-Dec;47(6):533-6.
Cardioversion of persistent atrial arrhythmia after treatment with venlafaxine in successful management of major depression and posttraumatic stress disorder
Finch SJ, van Zyl LT.
There is increasing evidence linking depression and cardiovascular disease. However, the authors could find no literature directly linking depression with atrial fibrillation or atrial flutter. The authors report the case of a patient with uncontrolled atrial arrhythmia who cardioverted to normal sinus rhythm after treatment of major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) with venlafaxine. The authors discuss comorbidity of MDD and atrial fibrillation, and explore evidence of venlafaxine as an antiarrhythmic agent. Further research is needed to establish the clinical role of venlafaxine as a Class 1 antiarrhythmic agent and any association between atrial arrhythmias and MDD and PTSD.

Clin Res Cardiol. 2007 Feb;96(2):114-8.
Atrial fibrillation in carcinoid heart disease: The role of serotonin. A review of the literature.
Langer C, Piper C, Vogt J, Heintze J, Butz T, Lindner O, Burchert W, Kersting C,
Horstkotte D.

J Mol Cell Cardiol. 2007 Jan;42(1):51-3.
5-hydroxytryptamine and atrial arrhythmogenesis: a “culprit mechanism” or bystander in patients with chronic atrial fibrillation?
Dobrev D.

43. Indian J Physiol Pharmacol. 1973 Apr-Jun;17(2):111-6.
Influence of 5-hydroxytryptamine on experimentally induced atrial arrhythmias in dogs.
Kuruvilla A, Aiman R.

Sov Med. 1972 Oct;35(10):30-3.
[Some aspects of the metabolism of biogenic monoamines (catecholamines and serotonin) in fibrillation arrhythmia treated by electrical impulses].
[Article in Russian]
Berestov AA, Safronova VI.

Klin Med (Mosk). 1971 Jan;49(1):25-9.
[Blood serotonin content during auricular fibrillation and its treatment by defibrillation].
[Article in Russian]
Panchenko VM, Kucherenko IA.

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“Selye’s demonstration of corn oil’s toxicity to the heart is an important link in the general picture of stress injury and adrenalin toxicity. The protective effects of saturated fats are not surprising when seen against the background of the toxic effects of adrenalin, causing the mobilization of fatty acids and the resulting lipid peroxidation.”

PUFA and arrhythmia:
Cardiovasc Res. 2007 Jan 15;73(2):386-94. Epub 2006 Oct 13.
Dietary n-3 fatty acids promote arrhythmias during acute regional myocardial ischemia in isolated pig hearts.
Coronel R, Wilms-Schopman FJ, Den Ruijter HM, Belterman CN, Schumacher CA, Opthof T, Hovenier R, Lemmens AG, Terpstra AH, Katan MB, Zock P.
OBJECTIVE:
Dietary supplementation with fish oil-derived n-3 fatty acids reduces mortality in patients with myocardial infarction, but may have adverse effects in angina patients. The underlying electrophysiologic mechanisms are poorly understood. We studied the arrhythmias and the electrophysiologic changes during regional ischemia in hearts from pigs fed a diet rich in fish oil.
METHODS:
Pigs received diets rich in fish oil, in sunflower oil, or a control diet for 8 weeks. Hearts were isolated and perfused. Ischemia was created by occluding the left anterior descending artery. Diastolic stimulation threshold, refractory period, conduction velocity, activation recovery intervals and the maximum downstroke velocity of 176 electrograms were measured in the ischemic zone. Spontaneous arrhythmias during 75 min of regional ischemia were counted.
RESULTS:
More episodes of spontaneous ischemia-induced sustained ventricular tachycardia and ventricular fibrillation occurred in the fish oil and sunflower oil group than in the control group. More inexcitable myocardium was present in the ischemic zone in the group fed fish oil or sunflower oil than in the control group after 20 min of ischemia. After 40 min of ischemia, more block occurred in the control group than in the other groups. The downstroke velocity of the electrograms in the ischemic border zone was lower in the fish oil group and sunflower oil group than in the control after 20 min.
CONCLUSIONS:
A diet rich in fish oil results in proarrhythmia compared to a control diet during regional ischemia in pigs. Myocardial excitability is reduced in the fish oil and sunflower oil group during the early phase of arrhythmogenesis. In the late phase of arrhythmogenesis, excitability is more reduced in the control group than in the fish oil and sunflower oil group.

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Progesterone protects against hemorrhagic shock, improves cardiovascular responses:

Crit Care Med. 2003 Jun;31(6):1786-93.
Progesterone administration after trauma and hemorrhagic shock improves cardiovascular responses.
Kuebler JF1, Jarrar D, Bland KI, Rue L 3rd, Wang P, Chaudry IH.
OBJECTIVE:
Studies have shown that female rats during the proestrus stage have significantly improved cell and organ functions after trauma-hemorrhage compared with male and ovariectomized females. This study investigated the hypothesis that progesterone can improve the depressed cardiovascular function in sex steroid-deficient female rats (i.e., ovariectomized females) after trauma-hemorrhage and resuscitation.
DESIGN:
Prospective study.
SETTING:
University laboratory.
SUBJECTS:
Ovariectomized female Sprague-Dawley rats (weight, 250-300 g).
INTERVENTIONS:
Rats underwent a 5-cm midline laparotomy (i.e., soft-tissue trauma), were bled to a mean arterial pressure of 35 mm Hg for approximately 90 mins, and were then resuscitated using Ringer’s lactate. A single dose of progesterone (25 mg/kg of body weight) or vehicle was administered subcutaneously during resuscitation.
MEASUREMENTS:
At 20 hrs after trauma-hemorrhage or sham operation, cardiac output and heart performance and the circulating blood volume were assessed using the indocyanine green dilution technique and a left ventricular catheter. Furthermore, the binding activity of progesterone receptors in nuclear extracts of left ventricular tissue was determined.
RESULTS:
Cardiac output, heart performance, and circulating blood volume were significantly decreased in vehicle-treated animals after trauma-hemorrhage. Administration of progesterone significantly improved cardiac output and heart performance and increased the circulating blood volume. This was associated with an increased progesterone receptor activity in the left ventricular nuclear extracts.
CONCLUSION:

Because administration of progesterone after trauma-hemorrhage in sex steroid-deficient females improved cardiovascular responses, this hormone seems to be a useful adjunct for the treatment of cardiovascular depression in postmenopausal and ovariectomized female trauma patients.

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Lactose Intolerance: Starch, Fructose, Sucrose, & Thyroid Status

Also see:
Hypothyroidism, Intestinal Bacterial Overgrowth, & Lactose Intolerance
Autoimmunity and Intestinal Flora
Thumbs Up: Fructose

Am J Physiol. 1995 Jun;268(6 Pt 1):G1066-73.
Diet-induced changes in gene expression of lactase in rat jejunum.
Goda T, Yasutake H, Suzuki Y, Takase S, Koldovský O.
To explore the mechanisms by which jejunal lactase activity is modified by carbohydrate and/or fat intake, mRNA levels and the absolute synthesis rate of lactase-phlorizin hydrolase (LPH) were determined in 6-wk-old rats that were fed either low-starch diets containing long-chain triacylglycerol (LCT, 73% energy as corn oil) or medium-chain triacylglycerol (MCT, 66% energy as MCT, 7% energy as corn oil), or a high-starch diet (70% energy as cornstarch) for 7 days. LPH mRNA levels in the jejunum were similar between LCT-fed and MCT-fed rats, but animals fed the high-starch diet exhibited a greater (2x) LPH mRNA level than other groups. The absolute synthesis rate of LPH, estimated by the flooding dose technique using [3H]phenylalanine, was greater (2.4x) in rats fed the high-starch diet than in other groups. A short-term force-feeding experiment revealed that sucrose was able to evoke LPH mRNA levels within 12 h but that a nonmetabolizable sugar (alpha-methylglucoside) was unable to enhance it. By contrast, animals fed the high-LCT diet showed a lower (by 30%) lactase activity than rats fed the low-starch, high-MCT diet, which was accompanied by not only a reduction of immunoreactive LPH in brush-border membranes but also a reduction in lactase activity per unit weight of immunoreactive LPH. These results suggest that both gene expression and posttranslational events of LPH might be influenced by dietary manipulations; carbohydrate intake primarily increases LPH mRNA levels, and LCT accelerates inactivation and/or degradation of lactase.

Biochem J. 1998 Apr 1;331 ( Pt 1):225-30.
Dietary carbohydrates enhance lactase/phlorizin hydrolase gene expression at a transcription level in rat jejunum.
Tanaka T, Kishi K, Igawa M, Takase S, Goda T.
We have previously shown that dietary sucrose stimulates the lactase/phlorizin hydrolase (LPH) mRNA accumulation along with a rise in lactase activity in rat jejunum [Goda, Yasutake, Suzuki, Takase and Koldovský (1995) Am. J. Physiol. 268, G1066-G1073]. To elucidate the mechanisms whereby dietary carbohydrates enhance the LPH mRNA expression, 7-week-old rats that had been fed a low-carbohydrate diet (5.5% of energy as starch) were given diets containing various monosaccharides or sucrose for 12h. Among carbohydrates examined, fructose, sucrose, galactose and glycerol elicited an increase in LPH mRNA accumulation along with a rise in lactase activity in the jejunum. By contrast, glucose and alpha-methylglucoside were unable to elicit a significant increase in LPH mRNA levels. To explore a transcriptional mechanism for the carbohydrate-induced increases in LPH mRNA levels, we employed two techniques currently available to estimate transcriptional rate, i.e. RNA protection assays of pre-mRNA using an intron probe, and nuclear run-on assays. Both assays revealed that fructose elicited an increase in transcription of the LPH gene, and that the transcription of LPH was influenced only slightly, if at all, by glucose intake. These results suggest that certain monosaccharides such as fructose or their metabolite(s) are capable of enhancing LPH mRNA levels in the small intestine, and that transcriptional control might play a major role in the carbohydrate-induced increase of LPH mRNA expression.

J Nutr Sci Vitaminol (Tokyo). 2006 Oct;52(5):347-51.
Dietary sucrose enhances intestinal lactase gene expression in euthyroid rats.
Kuranuki S, Mochizuki K, Goda T.
It is postulated that dietary carbohydrates and thyroid hormones are major regulators for expression of the lactase/phlorizin hydrolase (LPH) gene in rat jejunum. In this study, we investigated the effects of thyroid hormones and dietary sucrose on LPH gene expression and lactase activity in starved rats. Firstly, animals at 8 wk of age were fed a low-starch diet (5.5% energy as cornstarch) or high-starch diet (71% energy as cornstarch) for 7 d (experiment 1). The mRNA level of LPH as well as lactase activity significantly decreased in rats fed the low-starch diet as compared to those fed the high-starch diet. To investigate the effects of thyroid hormone status, the animals previously fed the low-starch diet were starved for 3 d, and half of the animals were given intraperitoneal (i.p.) injections of 20 microg/ 100 g body weight triiodothyronine (T3) twice daily (experiment 2). The LPH mRNA level and lactase activity were elevated by starvation for 3 d, but they were repressed by the injection of T3 during starvation. To investigate the effects of dietary sucrose in starved rats, they were force-fed a sucrose diet for 6 h (experiment 3). The LPH gene expression and lactase activity were up-regulated by force-feeding a sucrose diet, only when the animals were kept in euthyroid status by daily T3 administrations. In contrast, the sucrase-isomaltase mRNA levels and sucrase activity were unaffected by force-feeding the sucrose diet for both T3-treated and untreated starved rats. Our work suggests that dietary sucrose is capable of enhancing lactase gene expression in starved rats when they have a sustainable thyroid hormone level.

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How Vegetable Oils Replaced Animal Fats in the American Diet

In this excerpt from The Happiness Diet, discover how Procter & Gamble convinced people to forgo butter and lard for cheap, factory-made oils loaded with trans fat.

Book ExcerptBefore highways and before railroads, America conducted her commerce via steamship over water through a system of rivers, canals, and lakes. In the 1800s, Cincinnati was the heart of the developed United States. At the time it was known to the world as Porkopolis. That’s because not so long ago, the most widely consumed meat in this nation was swine. 

This was before refrigeration. The biggest enemy of 19th-century butchers was spoilage. Eating cows didn’t make a whole lot of sense: Distributing the meat of a freshly killed 1,500-pound animal before it went bad was difficult without roads and temperature-controlled trains. But pigs are fatty, which makes them excellent for salt curing because they don’t lose flavor.

Cincinnati is on the Ohio River, which flows to the Mississippi River, which leads to the ever-important port of New Orleans. From the mouth of the mighty Mississippi, Porkopolis distributed meat throughout the coastal southern United States. The by-products of pork production meant that the burgeoning metropolis was also home to many tanneries, boot makers, and upholsters. Animal fats were hot commodities, as they were rendered and molded into soap and candles. Breaking down pigs was a highly efficient process known as the disassembly line — an idea that would later be reverse-engineered by Henry Ford to produce automobiles.

A major economic depression in the 1870s caused two important citizens of Porkopolis to join forces in order to cut costs and survive the bear market. They formed a company that would eventually be responsible for the greatest dietary shift in our country’s history. William Procter brought his candle-making business to the states after a fire destroyed his business in England. James Gamble fled Ireland during the Great Potato Famine and became a soap manufacturer. In a twist of fate, the two men happened to marry sisters in Cincinnati. Together, the brothers-in-law formed Procter & Gamble, a soap- and candle-manufacturing operation.

“What was garbage in 1860 was fertilizer in 1870, cattle feed in 1880, and table food and many things else in 1890.” — Popular Science, on cottonseed

At the time, soap was sold in huge wheels that were sliced into custom-sized portions at general stores. Procter and Gamble decided to take a chance by mass-producing individually wrapped bars of soap. To pull this off, the brother-in-laws needed to drastically reduce the price of their raw ingredients, which meant finding a replacement for expensive animal fats. They settled on a mix of palm and coconut oils and created the first soap that floated in water — a handy invention when clothes and dishes alike were washed in a sudsy basin. Hard pressed to come up with a name for this new product, Procter looked to the bible for inspiration and found it in Psalm 45:8: “All thy garments smell of myrrh, and aloes, and cassia, out of the ivory palaces, whereby they have made thee glad.” The word Ivory was trademarked, and in short order Americans all over the country would know the purity of this soap.

Oddly enough, the company to thank for the fact that America now eats so much vegetable oil has never produced much in the way of food. Thanks to Procter & Gamble the United States boosted the production of a waste product of cotton farming, cottonseed oil. To ensure a steady, cheap supply for soap production the company formed a subsidiary in 1902 called Buckeye Cotton Oil Co. Before processing, cottonseed oil is cloudy red and bitter to the taste because of a natural phytochemical called gossypol (it’s used today in China as male birth control) and is toxic to most animals, causing dangerous spikes in the body’s potassium levels, organ damage, and paralysis.

An issue of Popular Science from the era sums up the evolution of cottonseed nicely: “What was garbage in 1860 was fertilizer in 1870, cattle feed in 1880, and table food and many things else in 1890.” But it entered our food supply slowly. It wasn’t until a new food-processing invention of hydrogenation that cottonseed oil found its way into the kitchens of America’s restaurants and homes.

Edwin Kayser, a German chemist, wrote to Procter & Gamble on October 18, 1907, about a new chemical process that could create a solid fat from a liquid. The company’s researchers had been interested in producing a solid form of cottonseed oil for years, and Kayser described his new process as “of the greatest possible importance to soap manufacturers.” The company purchased US rights to the patents and created a lab on the Procter & Gamble campus, known as Ivorydale, to experiment with the new technology. Soon the company’s scientists produced a new creamy, pearly white substance out of cottonseed oil. It looked a lot like the most popular cooking fat of the day: lard. Before long, Procter & Gamble sold this new substance (known today as hydrogenated vegetable oil) to home cooks as a replacement for animal fats.

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Procter & Gamble filed a patent application for the new creation in 1910, describing it as “a food product consisting of a vegetable oil, preferably cottonseed oil, partially hydrogenated, and hardened to a homogeneous white or yellowish semi-solid closely resembling lard. The special object of the invention is to provide a new food product for a shortening in cooking.” They came up with the name Crisco, which they thought conjured up crispness, freshness, and cleanliness.

Convincing homemakers to swap butter and lard for a new fat created in a factory would be quite a task, so the new form of food needed a new marketing strategy. Never before had Procter & Gamble — or any company for that matter — put so much marketing support or advertising dollars behind a product. They hired the J. Walter Thompson Agency, America’s first fullservice advertising agency staffed by real artists and professional writers. Samples of Crisco were mailed to grocers, restaurants, nutritionists, and home economists. Eight alternative marketing strategies were tested in different cities and their impacts calculated and compared. Doughnuts were fried in Crisco and handed out in the streets. Women who purchased the new industrial fat got a free cookbook of Crisco recipes. It opened with the line, “The culinary world is revising its entire cookbook on account of the advent of Crisco, a new and altogether different cooking fat.” Recipes for asparagus soup, baked salmon with Colbert sauce, stuffed beets, curried cauliflower, and tomato sandwiches all called for three to four tablespoons of Crisco.

Health claims on food packaging were then unregulated, and the copywriters claimed that cottonseed oil was healthier than animal fats for digestion. Advertisements in the Ladies’ Home Journal encouraged homemakers to try the new fat and “realize why its discovery will affect every family in America.” The unprecedented product rollout resulted in the sales of 2.6 million pounds of Crisco in 1912 and 60 million pounds just four years later. This new food bolstered the bottom line of a company whose other products were Ivory Soap, Lenox Soap, White Naphtha Laundry Soap, and Star Soap. It also helped usher in the age of margarine as well as low-fat foods.

Procter & Gamble’s claims about Crisco touching the lives of every American proved eerily prescient. The substance (like many of its imitators) was 50 percent trans fat, and it wasn’t until the 1990s that its health risks were understood. It is estimated that for every two percent increase in consumption of trans fat (still found in many processed and fast foods) the risk of heart disease increases by 23 percent. As surprising as it might be to hear, the fact that animal fats pose this same risk is not supported by science.

Reprinted from The Happiness Diet (c) 2011 by Drew Ramsey, MD and Tyler Graham. Permission granted by Rodale, Inc. Available wherever books are sold.

 

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Hypothyroidism Causes Shrinking of the Thymus Gland

Hypothyroidism causes the thymus gland to atrophy (Abou-Rabia and Kendall, 1994), partly because the thyroid hormone itself is essential for the maintenance of the gland, and also because hypothyroidism is likely to be accompanied by excessive levels of estrogen and cortisol. -Ray Peat, PhD

Cell Tissue Res 1994 Sep;277(3):447-SS.
Involution of the rat thymus in experimentally induced hypothyroidism.
AbouRabia N, Kendall MD.
The thymus, as part of the immune-neuroendocrine axis, is greatly influenced by factors from most endocrine glands, especially the thyroid. Antithyroid drugs (carbimazole and methimazole) were used to induce hypothyroidism in rats. Histological and ultrastructural examination of the thymus showed progressive thymic involution after 4 weeks of drug treatment to the end of observations (7 weeks). The involution was characterised by increased thymocyte apoptosis and thymocyte phagocytosis by macrophages. This resulted in thymocyte depopulation, increases in numbers of interdigitating cells, alterations to mainly subcapsular and medullary epithelial cells, an apparent increase of mast cells and collagen in the capsule and septa, and increased numbers of B cells and plasma cells. Lymphoid cells immuno-reactive with MRC OX12 (which detects B cells) were observed within blood vessel walls, suggesting that they may have been moving in and out of the thymus. The administration of drugs causing hypothyroidism, therefore, also caused marked involution of the thymus.

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Protected: Shut Your Mouth and Save Your Life

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Collection of Ray Peat Quote Blogs by FPS

Also see:
Collection of FPS Charts
Master List – Ray Peat, PhD Interviews

Ray Peat, PhD: Quotes Relating to Exercise

Ray Peat, PhD and Concentric Exercise

Ray Peat, PhD Quotes on Coconut Oil

Ray Peat, PhD Quotes on Therapeutic Effects of Niacinamide

Ray Peat, PhD on Carbon Dioxide, Longevity, and Regeneration

Ray Peat, PhD on Low Blood Sugar & Stress Reaction

Ray Peat, PhD on Thyroid, Temperature, Pulse, and TSH

Ray Peat, PhD on the Benefits of the Raw Carrot

Ray Peat, PhD on Aspirin

Ray Peat PhD on the Menstrual Cycle

Ray Peat, PhD on High Blood Pressure

Ray Peat, PhD on Endotoxin

Ray Peat, PhD on Brewer’s Yeast

Ray Peat, PhD on Nitric Oxide

Ray Peat, PhD – Concerns with Starches

Universal Principle of Cellular Energy

Protect the Mitochondria

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Serotonin Activates Glycolysis

Also see:
Tryptophan Metabolism: Effects of Progesterone, Estrogen, and PUFA
Estrogen Increases Serotonin
Hypothyroidism and Serotonin
Omega -3 “Deficiency” Decreases Serotonin Producing Enzyme
Enzyme to Know: Tryptophan Hydroxylase
Tryptophan, Sleep, and Depression
Carbohydrate Lowers Free Tryptophan
Gelatin > Whey
Serotonin, Fatigue, Training, and Performance
Gelatin, Glycine, and Metabolism
Whey, Tryptophan, & Serotonin
Serotonin and Melatonin Lower Progesterone
Role of Serotonin in Preeclampsia
Maternal Ingestion of Tryptophan and Cancer in Female Offspring
Melatonin Lowers Body Temperature

Serotonin activates glycolysis, forming lactic acid. Excess lactic acid tends to decrease efficient energy production by interfering with mitochondrial respiration. -Ray Peat, PhD

Mol Genet Metab. 1998 Mar;63(3):235-8.
Activation of membrane skeleton-bound phosphofructokinase in erythrocytes induced by serotonin.
Assouline-Cohen M, Ben-Porat H, Beitner R.
We show here that serotonin, both in vivo and in vitro, induced a marked activation of phosphofructokinase, the rate-limiting enzyme in glycolysis, in the membrane-skeleton fraction from erythrocytes. Concomitantly, the hormone induced a striking increase in lactate content, reflecting stimulation of glycolysis. The enzyme’s activity in the cytosolic (soluble) fraction remained unchanged. These results suggest a defense mechanism in the erythrocytes against the damaging effects of serotonin, whose concentration in plasma increases in many diseases and is implicated as playing an important role in circulation disturbances.

Mol Genet Metab. 2007 Dec;92(4):364-70. Epub 2007 Aug 27.
Serotonin stimulates mouse skeletal muscle 6-phosphofructo-1-kinase through tyrosine-phosphorylation of the enzyme altering its intracellular localization.
Coelho WS, Costa KC, Sola-Penna M.
Serotonin (5-HT) is a hormone implicated in the regulation of many physiological and pathological events. One of its most intriguing properties is the ability to up-regulate mitosis. Moreover, it has been shown that 5-HT stimulate glucose uptake on skeletal muscle, suggesting that 5-HT may regulate glucose metabolism of peripheric tissues. Here we demonstrate that 5-HT stimulates skeletal muscle 6-phosphofructo-1-kinase (PFK) activity in a dose-response manner, through 5-HT(2A) receptor subtype. Maximal activation of the enzyme (2.5-fold compared to control) is achieved in the presence of 25pM 5-HT, increasing both PFK maximal velocity and affinity for the substrate fructose-6-phosphate. These effects occur due to tyrosine phosphorylation of the enzyme that is 2-fold enhanced upon 5-HT stimulation of skeletal muscles preparation. Once 5-HT-induced tyrosine phosphorylation of PFK is prevented by genistein, a tyrosine kinase inhibitor, the hormone stimulatory effect on PFK is abrogated. Wortmannin, a phosphatidylinositol-3-kinase (PI3K) inhibitor, does not interfere on 5-HT-induced stimulation of PFK, supporting that the observed effects are independent on insulin signaling pathway. Furthermore, 5-HT promotes the association of PFK to the muscle f-actin, suggesting that the hormone alters PFK intracellular distribution, favoring its association to the cytoskeleton. Altogether, our results support evidences that 5-HT augments skeletal muscle glucose consumption through stimulation of glycolysis key regulatory enzyme, PFK, throughout tyrosine phosphorylation and intracellular redistribution of the enzyme.

Gen Pharmacol. 1994 Oct;25(6):1257-62.
Serotonin-induced decrease in brain ATP, stimulation of brain anaerobic glycolysis and elevation of plasma hemoglobin; the protective action of calmodulin antagonists.
Koren-Schwartzer N, Chen-Zion M, Ben-Porat H, Beitner R.
1. Injection of serotonin (5-hydroxytryptamine) to rats, induced a dramatic fall in brain ATP level, accompanied by an increase in P(i). Concomitant to these changes, the activity of cytosolic phosphofructokinase, the rate-limiting enzyme of glycolysis, was significantly enhanced. Stimulation of anaerobic glycolysis was also reflected by a marked increase in lactate content in brain. 2. Brain glucose 1,6-bisphosphate level was decreased, whereas fructose 2,6-bisphosphate was unaffected by serotonin. 3. All these serotonin-induced changes in brain, which are characteristic for cerebral ischemia, were prevented by treatment with the calmodulin (CaM) antagonists, trifluoperazine or thioridazine. 4. Injection of serotonin also induced a marked elevation of plasma hemoglobin, reflecting lysed erythrocytes, which was also prevented by treatment with the CaM antagonists. 5. The present results suggest that CaM antagonists may be effective drugs in treatment of many pathological conditions and diseases in which plasma serotonin levels are known to increase.

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Tryptophan Metabolism: Effects of Progesterone, Estrogen, and PUFA

Also see:
Estrogen Increases Serotonin
Hypothyroidism and Serotonin
Omega -3 “Deficiency” Decreases Serotonin Producing Enzyme
Enzyme to Know: Tryptophan Hydroxylase
Tryptophan, Sleep, and Depression
Carbohydrate Lowers Free Tryptophan
Gelatin > Whey
Serotonin, Fatigue, Training, and Performance
Gelatin, Glycine, and Metabolism
Whey, Tryptophan, & Serotonin
Serotonin and Melatonin Lower Progesterone
Role of Serotonin in Preeclampsia
Maternal Ingestion of Tryptophan and Cancer in Female Offspring
Melatonin Lowers Body Temperature

Pellagra occurs about twice as often in women as in men, and this is because estrogen activates an enzyme that alters metabolism of tryptophan, blocking the formation of niacin. The alternative products include the excitotoxin, quinolinic acid, and some carcinogens.

Progesterone inhibits the activity of that enzyme. Progesterone also lowers brain serotonin (Izquierdo, et al., 1978), decreases the excitatory carcinogens (Moursi, et al., 1970) and increases the formation of niacin (Shibata, et al., 2003) The polyunsaturated fats, DHA, EPA, and linoleic acid activate the conversion of tryptophan to quinolinic acid (Egashira, et al., 2003, 2007), and inhibit the formation of niacin (Egashira, et al., 1995). -Ray Peat, PhD

Pharmacol Res Commun. 1978 Jul;10(7):643-56.
Role of ACTH on the effect of medroxyprogesterone in brain stem serotonin.
Izquierdo JA, Savini C, Borghi E, Rabiller G, Costas S, Justel E.
A clinical study with 361 female rats was conducted to elucidate the mechanism whereby MPA (medroxyprogesterone acetate) lowers 5-HT/5-HIAA ratio in the brain area and the possible role of serotoniergic mechanisms. In addition, the participation of MAO (monoamino oxidase) system and the effects of some steroids were studied in order to establish a relationship between chemical structure and activity. The effects of the following steroids were studied: MPA (medroxyprogesterone acetate), melengestrol acetate, chlormadinone, pregnenolone, -methyl pregnenolone, DOCA, acetoxi-progesterone, and ACTH (synacthen). Effects of these substances on LTP (liver tryptophan pyrrolase) activity, total and free plasma and brain stem Trp (tryptophan), and the 5HT and 5HTAA content in brain stem are tabulated. Of all the substances, only MPA and melengestrol acetate significantly raised LTP activity and both also lowered 5-HT content of brain stem. The high levels of ACTH in the blood of the adrenalectomized rats, as in those under fasting conditions, antagonized MPA effects. To further test this seeming result, ACTH and ACTH-MPA were injected into another group of animals. The ACTH not only increased plasma corticosterone but also antagonized the effect of MPA on the 5-HT content of brain stem. The study did not identify a relationship between chemical structure of the steroids studied and effects observed.

Biosci Biotechnol Biochem. 1997 Jul;61(7):1200-2.
Effects of sex hormones on the metabolism of tryptophan to niacin and to serotonin in male rats.
Shibata K, Toda S.
It is known that deaths attributable to pellagra, which is considered to be a disease caused by the disturbance of tryptophan metabolism, have been approximately two-fold higher in women than in men. We investigated the effects of the administration of female and male sex hormones on the contents of tryptophan and such metabolites as serotonin, nicotinamide, N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide, and N1-methyl-4-pyridone-3-carboxamide, and on the conversion ratio of tryptophan to niacin in male rats. Feeding a diet containing estrone or testosterone had no effect on the concentrations of tryptophan and serotonin in the blood and brain, or on the concentration of 5-hydroxyindole-3-acetic acid in the brain. On the contrary, feeding a diet containing estrone caused to a decrease in the urinary excretion of nicotinamide, N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide, and N1-methyl-4-pyridone-3-carboxamide, and of the conversion ratio of tryptophan to niacin when compared with the control rats. Feeding a diet containing testosterone had no effect on any parameter. We postulate from these findings that the cause of higher pellagra deaths in women than in men is attributable to the decrease in the formation of niacin from tryptophan, but not in the formation of serotonin by the female hormone. It seems likely that female sex hormones inhibit the synthesis of niacin from tryptophan, and that women, especially during pregnancy, will be more at risk to pellagra than are men.

Bull World Health Organ. 1970;43(5):651-61.
The influence of sex, age, synthetic oestrogens, progestogens and oral contraceptives on the excretion of urinary tryptophan metabolites.
Moursi GE, Abdel-Daim MH, Kelada NL, Abdel-Tawab GA, Girgis LH.
The excretion of urinary tryptophan metabolites was studied in normal and postmenopausal women and in women taking norethindrone and ethinyl estradiol, singly and in combination. The results showed that the altered tryptophan metabolism found in the preovulatory phase of the cycle and in postmenopausal women was the result of an interaction between Vitamin-B6 and endogenous sex hormones. During the preovulatory phase, endogenous estradiol disrupted the normal activity of the Vitamin-B6-dependent quinolinic acid decarboxylase, which resulted in the accumulation of bladder carcinogens in urine. During the postovulatory phase, endogenous progesterone and the production of metabolites antagonized this effect. Administration of naturally occurring progesterone and of ethinyl estradiol, alone and in combination with norethindrone, was able to counter the interaction between Vitamin-B6 and endogenous estradiol. It is suggested that the cyclic excretion pattern of endogenous bladder carcinogens in young, nonpregnant women may contribute, in part, to the low incidence of bladder cancer in women.

Br J Nutr. 1984 Mar;51(2):219-24.
Inhibition of tryptophan metabolism by oestrogens in the rat: a factor in the aetiology of pellagra.
Bender DA, Totoe L.
The effect of the administration of oestrone sulphate on tryptophan metabolism has been assessed in rats in order to determine whether and to what extent inhibition of tryptophan metabolism by oestrogens may be a factor in the aetiology of pellagra, and might explain the reported twofold excess of females over males in many outbreaks of pellagra. Feeding ovariectomized rats for 1 week on a diet containing 15 mg oestrone sulphate/kg led to significant inhibition of kynurenine hydroxylase (EC 1.14.13.9), kynureninase (EC 3.7.1.3) and 3-hydroxyanthranilate oxidase (EC 1.13.11.6). There was also a significant increase in plasma tryptophan, suggesting decreased activity of tryptophan oxygenase (EC 1.13.11.11). This inhibition of tryptophan metabolism will result in a considerable reduction in the synthesis of the nicotinamide nucleotide coenzymes (NAD and NADP) from tryptophan. When ovariectomized rats were maintained for 4 weeks on a diet providing no preformed niacin and only a marginally adequate amount of tryptophan (1030 mg/kg), the addition of sulphate to the diet led to a significant reduction in the liver content of nicotinamide nucleotides and the urinary excretion of the end-product of NAD metabolism, N1-methyl nicotinamide. It is suggested that when the diet is only marginally adequate in tryptophan and niacin, inhibition of tryptophan metabolism by endogenous or administered oestrogens may be an additional factor in the development of pellagra.

Br J Nutr. 1982 May;47(3):609-14.
Effects of oestrogen administration on vitamin B6 and tryptophan metabolism in the rat.
Bender DA, Tagoe CE, Vale JA.
1. In order to assess the effects of oestrogens on the metabolism of tryptophan and vitamin B6, ovariectomized rats have been maintained on diets providing known amounts of tryptophan, nicotinamide and vitamin B6. They received oestrone sulphate, 210 micrograms/kg body-wt per d, either incorporated in the diet for 8 weeks, or by daily intraperitoneal injection for periods of 1-3 d. 2. Oestrone sulphate administration caused a slight reduction in the concentration of pyridoxal phosphate in plasma. It had no effect on the concentration of pyridoxal phosphate in liver or kidney, the urinary excretion of 4-pyridoxic acid, the activation of erythrocyte aspartate aminotransferase (L-aspartate:2-oxo-glutarate aminotransferase, EC 2. 6. 1. 1) by incubation with added pyridoxal phosphate, or the activity of pyridoxal oxidase (aldehyde:oxygen oxido-reductase, EC 1.2.3.1) in the liver. 3. Oestrone sulphate administration caused an increase in the urinary excretion of kynurenine and a reduction in the activity of liver kynureninase (L-kynurenine hydrolase, EC 3.7.1.3). It had no effect on the urinary excretion of N1-methyl nicotinamide or the concentrations of nicotinamide nucleotides in blood, liver or kidney. 4. There was a considerable excess of the apoenzyme of kynureninase in the liver. Incubation of liver homogenates with added pyridoxal phosphate led to a 4- to 5-fold increase in activity. 5. We conclude that there is no evidence of any significant effect of oestrogens on vitamin B6. It is suggested that abnormalities of tryptophan metabolism in women receiving oestrogens, which have been widely attributed to drug-induced vitamin B6 depletion, can be accounted for by inhibition of kynureninase by oestrogen metabolites.

Adv Exp Med Biol. 2003;527:435-41.
Increase in conversion of tryptophan to niacin in pregnant rats.
Shibata K, Fukuwatari T, Murakami M, Sasaki R.
There is the report that the deaths by pellagra in women is approximately twofold excess that in men. In the present experiment, in order to clarify a factor in the etiology of pellagra in female and to get basic information how much niacin should be supplemented in pregnant state, we investigated the effects of pregnant on the metabolism of tryptophan to niacin in rats. The daily urine samples were collected from day -17 and day +6 (the delivery day was designated as day 0) and the intermediates of tryptophan to niacin were measured. The metabolites such as kynurenic acid, xanthurenic acid, anthranilic acid, 3-hydroxyanthranilic acid, quinolinic acid, N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide, N1-methyl-4-pyridone-3-carboxamide were increased with progress in pregnant and returned to normal levels after the delivery. The catabolism of tryptophan is accelerated during pregnancy, indicataing that pregnancy would not be an etiology of pellagra and no niacin supplement needs but tryptohan supplement would need.

Biochim Biophys Acta. 2004 Nov 8;1686(1-2):118-24.
Differential effects of dietary fatty acids on rat liver alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase activity and gene expression.
Egashira Y, Murotani G, Tanabe A, Saito K, Uehara K, Morise A, Sato M, Sanada H.
Hepatic alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD; formerly termed picolinic carboxylase) [EC4.1.1.45] plays a key role in regulating NAD biosynthesis and the generation of quinolinate (quinolinic acid) from tryptophan. Quinolinate is a potent endogenous excitotoxin of neuronal cells. We previously reported that ingestion of fatty acids by rats leads to a decrease in their hepatic ACMSD activity. However, the mechanism of this phenomenon is not clarified. We previously purified ACMSD and cloned cDNA encoding rat ACMSD. Therefore, in this study, we examined the differential effect of fatty acids on ACMSD mRNA expression by Northern blot. Moreover, we measured quinolinic acid concentration in rats fed on fatty acid. When diets containing 2% level of fatty acid were given to male Sprague-Dawley rats (4 weeks old) for 8 days, long-chain saturated fatty acids and oleic acid did not affect ACMSD mRNA expression in the liver. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) strongly suppressed the liver ACMSD mRNA expression. In rats fed with high linoleic acid diet for 8 days, serum quinolinic acid was significantly increased as compared with the rats fed on a fatty acid-free diet under the condition of the approximately same calorie ingestion. These results suggest that the transcription level of ACMSD is modulated by polyunsaturated fatty acids, and suppressive potency of ACMSD mRNA is n-3 fatty acid family>linoleic acid (n-6 fatty acid)>saturated fatty acid. Moreover, this study provides the information that a high polyunsaturated fatty acid diet affects the production of quinolinic acid in serum by suppressing the ACMSD activity.

Int J Vitam Nutr Res. 2007 Mar;77(2):142-8.
Dietary protein level and dietary interaction affect quinolinic acid concentration in rats.
Egashira Y, Sato M, Saito K, Sanada H.
During tryptophan-niacin conversion, hepatic alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) [EC4.1.1.45] plays a key role in regulating NAD biosynthesis. ACMSD activity is greatly affected by many factors such as nutritional status and disease. The tryptophan catabolite quinolinic acid has been reported to be associated with the pathogenesis of various disorders and is a potential endogenous toxin. However the effects of dietary protein levels or dietary interaction between protein levels and fatty acid type to this process have not been investigated and are still unknown. In this study, we examined whether dietary protein level, fatty acid type, namely saturated fatty acid and polyunsaturated fatty acid, and their interaction affect serum quinolinic acid concentration in rats. Male Sprague-Dawley rats (4-weeks old) were fed with 20% casein + 10% stearic acid diet (20C10S), 20% casein + 10% linoleic acid diet (20C10L), 40% casein + 10% stearic acid diet (40C10S), or 40% casein + 10% linoleic acid diet (40C10L) for 8 days, and serum quinolinic acid concentration and ACMSD activity were determined. Serum quinolinic acid concentration was significantly increased in the 40C10L group compared with other three groups. There was also the negative correlation between the sum of liver and kidney ACMSD activities, and serum quinolinic acid concentration per tryptophan intake (r = 0.8209, p < 0.01). Increased serum QA concentrations are probably due to a decreased ACMSD activity.

Comp Biochem Physiol A Physiol. 1995 Aug;111(4):539-45.
Effect of dietary linoleic acid on the tryptophan-niacin metabolism in streptozotocin diabetic rats.
Egashira Y, Nakazawa A, Ohta T, Shibata K, Sanada H.
To make clear the mechanism of change of tryptophan-niacin metabolism in diabetic rats, we investigated the effect of dietary linoleic acid on the tryptophan-niacin metabolites and the activity of liver, alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD), a key enzyme of tryptophan-niacin metabolism, in streptozotocin diabetic rats. Moreover, we investigated the involvement of linoleic acid in the induction of hepatic ACMSD activity by streptozotocin diabetes. In diabetic rats, the sum of urinary excretion of nicotinamide, N1-methylnicotinamide (MNA), N1-methyl-2-pyridone-5-carboxamide (2-Py) and N1-methyl-4-pyridone-3-carboxamide (4-Py) was higher in the fat free diet group than in the linoleic acid group, that was accompanied by the increase of tryptophan intake and reduction of body weight in the fat free diet group. In diabetic rats, hepatic ACMSD activity was higher in the fat free diet group than in the linoleic acid group. The results indicated that the induction of hepatic ACMSD activity by diabetes was not due to removal of the suppressive effect of the linoleic acid on the enzyme. In the diabetic+insulin group, hepatic ACMSD activity was significantly lower than in the diabetic group.

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Adverse Effects of Mouth Breathing

Also see:
The Nose Knows: A Case for Nasal Breathing During High Intensity Exercise
Breathing, CO2, Performance, and Health
A Common Finding – Altered Respiration
Hyperventilation and Breathe-More Myth
GOOD BREATHING, BAD BREATHING
Carbon Dioxide Basics
Protective Altitude
Chronic hyperventilation; have you got it, what is it, and how do you fix it?
Phospholipases, PUFA, and Inflammation
Estrogen’s Role in Asthma
Unsaturated Fats and Lung Function
Bohr Effect and Cells O2 Levels: Healthy vs. Sick People

J Laryngol Otol. 1987 Jun;101(6):558-63.
Rediscovering the importance of nasal breathing in sleep or, shut your mouth and save your sleep.
Lavie P.
Recent research, stimulated by the growing awareness of the sleep apnea syndrome, has shown that nasal breathing plays a major role in the regulation of respiration in sleep. These observations are not new; they confirm century-old clinical findings on the importance of nasal breathing in sleep. The earliest account of the deleterious effects of mouth breathing in sleep was made by Lemnious Levinus towards the end of the sixteenth century. Two hundred years later, Catlin dedicated an entire book to the superiority of nasal breathing over mouth breathing in sleep; and in the late 1800’s, Cline, Wells, Griffin and others showed that obstructed nasal breathing causes sleep disorders.

Am J Rhinol. 2005 Nov-Dec;19(6):607-11.
Nasal congestion and hyperventilation syndrome.
Bartley J.
This article evaluates the prevalence of hyperventilation syndrome (HVS) in patients who continue to complain of ongoing nasal congestion, despite an apparently adequate surgical result and appropriate medical management.
METHODS:
Prospective case series of 14 patients from June 2002 to October 2003 was performed. Patients, who presented complaining of nasal congestion after previous nasal surgery and who appeared to have an adequate nasal airway with no evidence of nasal valve collapse, were evaluated for HVS. When appropriate, nasal steroids and oral antihistamines also had been tested without success. Three patients had end-tidal P(CO2) levels measured and five patients underwent breathing reeducation.
RESULTS:
All patients had an elevated respiratory rate (>18 breaths/minute) with an upper thoracic breathing pattern. Twelve of the 14 patients complaining of nasal obstruction had an elevated Nijmegen score indicative of HVS. An average number of 2.5 procedures had been performed on each patient. End-tidal P(CO2) levels were < or = 35 mmHg in the three patients who had expired P(CO2) levels measured. Breathing retraining was successful in correcting the nasal congestion in two of five patients. CONCLUSION: HVS should be included in the differential diagnosis of patients presenting with nasal congestion, particularly after failed nasal surgery. One possible explanation is increased nasal resistance secondary to low arterial P(CO2) levels. Another possible explanation is reduced alae nasae muscle activity secondary to the reduced activity of serotonin-containing raphe neurons. Additional surgery may not necessarily be the answer in HVS patients complaining of nasal congestion.

Gen Dent. 2010 Jan-Feb;58(1):18-25; quiz 26-7, 79-80.
Mouth breathing: adverse effects on facial growth, health, academics, and behavior.
Jefferson Y.
The vast majority of health care professionals are unaware of the negative impact of upper airway obstruction (mouth breathing) on normal facial growth and physiologic health. Children whose mouth breathing is untreated may develop long, narrow faces, narrow mouths, high palatal vaults, dental malocclusion, gummy smiles, and many other unattractive facial features, such as skeletal Class II or Class III facial profiles. These children do not sleep well at night due to obstructed airways; this lack of sleep can adversely affect their growth and academic performance. Many of these children are misdiagnosed with attention deficit disorder (ADD) and hyperactivity. It is important for the entire health care community (including general and pediatric dentists) to screen and diagnose for mouth breathing in adults and in children as young as 5 years of age. If mouth breathing is treated early, its negative effect on facial and dental development and the medical and social problems associated with it can be reduced or averted.

Cien Saude Colet. 2010 Mar;15(2):437-44.
[Prevalence of mouth breathing in children from an elementary school].
[Article in Portuguese]
Felcar JM, Bueno IR, Massan AC, Torezan RP, Cardoso JR.
The objective of this article is to identify the prevalence of mouth breathing in children from an elementary school. 496 questionnaires were answered by 1st and 4th grade children’s parents or sponsors in order to identify mouth-breathing. There were questions about habits, sleeping, behavior, eating, personal care and breathing. Mann-Whitney and the Chi-square tests were used to compare the variables between mouth-breathing and nose-breathing among the groups. To measure the exposure effect of the explanatory variables on mouth breathing, the test of logistic regression was used and its magnitude was calculated through Odds Ratio. The statistical significance was set at 5%, and the rate of returned questionnaires was 84.5%. The prevalence of the mouthbreathing over this population was 56.8%. The average age was 7 years old (6-9). There was no significant statistical difference between genders, considering 49.1% male and 50.9% female. The final model of logistic regression identified the variables dribble, sleeps well (negative association) and snores as factors that predict the occurrence of the mouth-breathing. The prevalence of mouthbreathing was similar to related in the literature. The variables dribble, sleeps well (negative association) and snores may be factors that predict the occurrence of mouth-breathing.

Int J Orofacial Myology. 2009 Nov;35:44-54.
Quantitative evaluation of the orofacial morphology: anthropometric measurements in healthy and mouth-breathing children.
Cattoni DM, Fernandes FD, Di Francesco RC, De Latorre Mdo R.
The anthropometric orofacial measurements of mouth-breathing children were compared to those of children with no history of speech-language disorders, according to age. Methods: 100 children participated, both males and females, with ages ranging from 7 to 11 years and 11 months, leukoderm, in mixed dentition period, with a mouth-breathing diagnosis. The control group was comprised of 254 children, of both sexes, with ages ranging from 7 to 11 years and 11 months, leukoderm, in mixed dentition period, with no history of speech-language disorders. The control group did not demonstrate any mouth-breathing. The children were submitted to anthropometric assessment and the orofacial measurements obtained were upper lip, lower lip, philtrum, upper face, middle face, lower face, and sides of the face. The instrument used was the electronic digital sliding caliper Starrett Series 727. There was statistically significant difference between the majority of the orofacial measurements of mouth-breathing children and the measurements of children with no history of speech-language disorders. Some orofacial measurements were different in the studied populations. The possibility of comparing orofacial measurements of children with and without mouth-breathing behavior allows the clinician to determine normal and altered structures of the orofacial morphology. The main advantages of the anthropometry are its noninvasive nature, its technological simplicity, low cost and objective analysis. The anthropometric procedures also have clinical applications in myofunctional assessment and therapy.

Int J Orofacial Myology. 2000 Nov;26:13-23.
Relationship between mouth breathing and postural alterations of children: a descriptive analysis.
Krakauer LH, Guilherme A.
The research within this article seeks to verify and demonstrate the consequences of mouth breathing versus nasal respiration and to view supposed postural alterations in groups of children within specific age ranges. The authors state that children with nasal respiration, age 8 and above, present with better posture than those who continue oral breathing beyond age 8. The importance of picture documentation is stressed in order to provide the most information regarding postural changes. A review of research and literature is provided in the article.

Orthod Fr. 2000 Jan;71(1):27-35.
[Could mouth breathing lead to obstructive sleep apnea syndromes. A preliminary study].
[Article in French]
Raskin S, Limme M, Poirrier R.
The aim of this preliminary work is to determine an easy method to diagnose “buccal breather” children and “nasal breather” children. Then, to establish a possible connection with the syndrome of obstructive sleep apnea. 22 children agreed to participate. Clinical, orthophonic, orthodontic, postural and polysomnographical exams have been carried out. The proposed clinical exam turns out to be a good means of diagnosing between buccal breathers and nasal breathers. The aerophonoscope reveals velar inadequacies in buccal breathers. The latter also present osseous discrepancies mainly in the mandible. The polysomnography reveals a higher apnea/hypopnea index and more agitated sleep in buccal breathers. Mandibular lowering movements are more frequent and similar to those of adults suffering from apnea. These elements similar to those encountered in adults suffering from apnea make us think that buccal breathing could be the origin of obstructive sleep apnea, several decades later.

Int J Pediatr Otorhinolaryngol. 2010 Sep;74(9):1021-7. Epub 2010 Jun 20.
Craniocervical posture and hyoid bone position in children with mild and moderate asthma and mouth breathing.
Chaves TC, de Andrade e Silva TS, Monteiro SA, Watanabe PC, Oliveira AS, Grossi DB.
INTRODUCTION:
The objective of the present study was to assess the craniocervical posture and the positioning of the hyoid bone in children with asthma who are mouth breathers compared to non-asthma controls.
METHODS:
The study was conducted on 56 children, 28 of them with mild (n=15) and moderate (n=13) asthma (14 girls aged 10.79+/-1.31 years and 14 boys aged 9.79+/-1.12 years), matched for sex, height, weight and age with 28 non-asthma children who are not mouth breathers. The sample size was calculated considering a confidence interval of 95% and a prevalence of 4% of asthma in Latin America. Eighteen variables were analyzed in two radiographs (latero-lateral teleradiography and lateral cervical spine radiography), both obtained with the head in a natural position. The independent t-test was used to compare means values and the chi-square test to compare percentage values (p<0.05). Intraclass correlation coefficient (ICC) was used to verify reliability.
RESULTS:
The Craniovertebral Angle (CVA) was found to be significantly smaller in asthma than in control children (106.38+/-7.66 vs. 111.21+/-7.40, p=0.02) and the frequency of asthma children with an absent or inverted hyoid triangle was found to be significantly higher compared to non-asthma children (36% vs. 7%, p=0.0001). The values of the inclination angles of the superior cervical spine in relation to the horizontal plane were significantly higher in moderate than in mild asthma children (CVT/Hor: 85.10+/-7.25 vs. 90.92+/-6.69, p=0.04 and C1/Hor: 80.93+/-5.56 vs. 85.00+/-4.20, p=0.04).
CONCLUSIONS:
These findings revealed that asthma children presented higher head extension and a higher frequency of changes in hyoid bone position compared to non-asthma children and that greater the asthma severity greater the extension of the upper cervical spine.

J Clin Pediatr Dent. 1995 Spring;19(3):191-4.
Hyoid bone and atlas vertebra in established mouth breathers: a cephalometric study.
Kumar R, Sidhu SS, Kharbanda OP, Tandon DA.
The position of hyoid bone and atlas vertebra in 29 established mouth breathers (17 boys and 12 girls) in the age group of 10-14 years were cephalometrically evaluated and compared with 23 nose breathers (11 boys and 12 girls). The children of both the groups were selected on the basis of history and clinical examination. The comparisons were made using univariate analysis for male and female groups separately as well as combined. It was observed that mouth breathers do maintain an extended head posture, which was evident from a decrease in distance between the occiput and dorsal arch of atlas vertebra. However the results of the present study did not reveal any distinct characteristics of hyoid bone and atlas vertebra that can be used to predict or associate the craniofacial pattern of mouth breathers.

J Clin Sleep Med. 2009 Dec 15;5(6):554-61.
Polysomnographic findings are associated with cephalometric measurements in mouth-breathing children.
Juliano ML, Machado MA, de Carvalho LB, Zancanella E, Santos GM, do Prado LB, do Prado GF.
OBJECTIVES:
Children with adenotonsillar hypertrophy and those with an abnormal craniofacial morphology are predisposed to having sleep disordered breathing; many of these children are mouth breathers. The aim of this study was to determine whether an association exists between polysomnographic findings and cephalometric measures in mouth-breathing children.
METHODS:
Twenty-seven children (15 mouth-breathing children and 12 nose-breathing children [control subjects]), aged 7 to 14 years, took part in the study. Polysomnographic variables included sleep efficiency, sleep latency, apnea-hypopnea index, oxygen saturation, arousal index, number of periodic limb movements in sleep, and snoring. Cephalometric measures included maxilla and mandible position, occlusal and mandibular plane inclination, incisor position, pharyngeal airway space width, and hyoid bone position.
RESULTS:
As compared with nose-breathing children, mouth breathers were more likely to snore (p < 0.001) and to have an apnea-hypopnea index greater than 1 (p = 0.02). Mouth-breathing children were also more likely to have a retruded mandible, more inclined occlusal and mandibular planes, a smaller airway space, and a smaller superior pharyngeal airway space (p < 0.01). The apnea-hypopnea index increased as the posterior airway space decreased (p = 0.05).
CONCLUSIONS:
Our study showed an association between polysomnographic data and cephalometric measures in mouth-breathing children. Snoring was the most important variable associated with abnormal craniofacial morphology. Orthodontists should send any mouth-breathing child for an evaluation of sleep if they find that the child has a small superior pharyngeal airway space or an increased ANB (the relationship between the maxilla and mandible), NS.PIO (occlusal plane inclination in relationship to the skull base), or NS.GoGn (the mandibular plane inclination in relation to the skull base), indicating that the child has a steeper mandibular plane.

J Pediatr (Rio J). 2010 May-Jun;86(3):202-8. Epub 2010 May 6.
The impact of speech therapy on asthma and allergic rhinitis control in mouth breathing children and adolescents.
Campanha SM, Fontes MJ, Camargos PA, Freire LM.
OBJECTIVE:
To determine the impact of speech therapy on asthma and allergic rhinitis control in mouth breathing children and adolescents.
METHODS:
This was a quasi-experimental randomized study of 24 mouth breathing patients with asthma and allergic rhinitis, aged from 6 to 15 years. All patients were taking beclomethasone diproprionate through oral inhalation at the start of the study. At enrollment on the study, oral inhalation was substituted with exclusively nasal inhalation and 1 month later half of the patients began speech therapy. They attended 16 speech therapy sessions in 8 weeks and continued taking beclomethasone dipropionate through exclusively nasal inhalation (BDT group). The comparison group received only beclomethasone diproprionate through exclusively nasal inhalation (BDI group). Both groups were assessed five times. Clinical scores were calculated for allergic rhinitis and asthma, an adapted version of the Marchesan orofacial myofunctional assessment protocol was applied, and parents/guardians’ observations were recorded, in addition to spirometry measurements of peak inspiratory and peak expiratory flow.
RESULTS:
There were significant improvements in the BDT group: clinical asthma score at T5 (p = 0.046); peak inspiratory flow at T4 (p = 0.030); peak expiratory flow at T3 (p = 0.008); breathing mode and lip position (p = 0.000) from T3 onwards; and parents/guardians’ observations at T2, T4, and T5 (p = 0.010; p = 0.027; p = 0.030).
CONCLUSIONS:
Speech therapy in combination with beclomethasone diproprionate through exclusively nasal inhalation resulted in earlier and longer-lasting clinical and functional control of asthma, allergic rhinitis, and mouth breathing than was achieved in the group that only took beclomethasone diproprionate.

Clinics (Sao Paulo). 2011;66(6):939-42.
Association between halitosis and mouth breathing in children.
Motta LJ, Bachiega JC, Guedes CC, Laranja LT, Bussadori SK.
OBJECTIVE:
To determine whether there is a correlation between halitosis and mouth breathing in children.
STUDY DESIGN:
Fifty-five children between 3 and 14 years of age were divided into two groups (nasal and mouth breathing) for the assessment of halitosis. A descriptive analysis was conducted on the degree of halitosis in each group. The chi-square test was used for comparison between groups, with a 5% level of significance.
RESULTS:
There was a significantly greater number of boys with the mouth-breathing pattern than girls. A total of 23.6% of the participants had no mouth odor, 12.7% had mild odor, 12.7% had moderate odor and 50.9% had strong odor. There was a statistically significant association between halitosis and mouth breathing.
CONCLUSIONS:
The occurrence of halitosis was high among the children evaluated, and there was a statistically significant association between halitosis and mouth breathing.

Braz J Otorhinolaryngol. 2006 May-Jun;72(3):394-9.
Prevalence and factors related to mouth breathing in school children at the Santo Amaro project-Recife, 2005.
De Menezes VA, Leal RB, Pessoa RS, Pontes RM.
AIM:
To determine the prevalence of mouth breathing children at the santo amaro project/ esef/ upe, and study their main facial and behavior alterations.
STUDY DESIGN:
transversal study.
MATERIAL AND METHODS:
there were 150 children in the sample, with ages ranging from 8 to 10 years. Data was collected by means of a questionnaire and clinical examinations. As for their breathing assessment, two tests were carried out: test 1- breath steam against a mirror; and test 2 -water remains in the mouth with lips closed for 3 minutes.
RESULTS:
mouth breathing prevalence was of 53.3%. There was no significant difference between gender, age and type of breathing. Facial alterations were:incomplete lip closure ( 58.8%X5,7%), fallen eyes ( 40.0%X1.4%), High palate ( 38.8%X2.9%), Anterior open bite ( 60.0% Versus 30.0%), Hypotonic lips ( 3.8%X0.0%), Circles under the eyes (97.5% Versus 77.1%).
CONCLUSION:
high mouth breathing prevalence without significant statistical difference between genders,age and type of mouth breathing. There was no association between behavior characteristics and type of breathing. There were significant differences between physical traits and breathing pattern.

Otolaryngol Head Neck Surg. 1981 Sep-Oct;89(5):804-10.
Sleep and breathing disturbance secondary to nasal obstruction.
Olsen KD, Kern EB, Westbrook PR.
The purpose of this study was to determine the effect of acute nasal obstruction on sleep and breathing in eight normal persons. The subjects were randomized into two groups. One night the subject was studied with the nose open and a second night with the nose obstructed. The electroencephalogram, electrocardiogram, inspiratory effort, nasal and oral airflow, and oxygen saturation were monitored. Sleep proved to be both subjectively and objectively disturbed. The subjects with the nose obstructed awoke more often, had a greater number of changes in sleep stage, had a prolongation of rapid-eye-movement (REM) latency, and spent a greater amount of time in stage I non-REM sleep (light sleep). Acute nasal obstruction caused a statistically significant increase in the number of partial and total obstructive respiratory events (obstructive hypopnea and obstructive apnea). Sleep apnea developed in one subject during this study merely on the basis of acute nasal obstruction.

Am Rev Respir Dis. 1981 Aug;124(2):158-60.
Disturbed sleep and prolonged apnea during nasal obstruction in normal men.
Zwillich CW, Pickett C, Hanson FN, Weil JV.
Anecdotal observations suggested that poor quality of sleep is a frequent complaint during upper respiratory infections (URI). Nasal obstruction occurs frequently during URI and causes sleep apnea in some infants. Sleep apnea disrupts normal sleep and could explain the complaints of poor sleep quality during URI in adults. Accordingly, 10 normal men had full night recordings of sleep stages and breathing rhythm before and during nasal obstruction. The order of obstructed and nonobstructed nights was randomized after a standard acclimatization night. During nasal obstruction, time spent in the deep sleep stages decreased from 90 +/- 11.2 (SEM) to 71 +/- 12.9 min (p less than 0.05), whereas significantly more time was spent in Stage 1 sleep (p less than 0.03). This loss of deep sleep during obstruction was associated with a twofold increase in sleep arousals and awakening (p less than 0.01) resulting from an increased (p less than 0.02) number of apneas (34 +/-19 during control sleep versus 86 +/- 34 during obstructed sleep). Apneas of 20 to 39 s in duration became 2.5 times more frequent (p less than 0.05) during obstruction. Oxygen saturation was studied in the last 4 subjects using an ear oximeter. Desaturation (SaO2 less than 90%) occurred 27 times during control sleep compared with 255 times during obstructed sleep. These desaturation episodes occurred only during apneas. All men complained of poor sleep quality during nasal obstruction. We concluded that apneas, sleep arousals and awakenings, and loss of deep sleep occur during nasal obstruction and may explain complaints of poor sleep quality during URI.

J Pediatr (Rio J). 2011 Jul-Aug;87(4):357-63. Epub 2011 Jul 18.
Assessment of the body posture of mouth-breathing children and adolescents.
Conti PB, Sakano E, Ribeiro MA, Schivinski CI, Ribeiro JD.
OBJECTIVE:
To investigate associations between mouth breathing (MBr), nose breathing (NBr) and body posture classification and clinical variables in children and adolescents, by comparing patients with mouth breathing syndrome with a control group of similar age.
METHODS:
This was an observational, analytical, controlled, cross-sectional study conducted at a university hospital. Children aged 5 years or more were recruited to one of two groups: healthy controls (NBr) or an MBr group. The MBr group comprised patients with a diagnosis of mouth breathing syndrome confirmed by clinical examination by a physician plus nasal endoscopy. The control group comprised healthy volunteers of the same age, with NBr confirmed by medical examination. All participants underwent postural assessment. Data were analyzed using the Mann-Whitney nonparametric test, the chi-square test and Fisher’s exact test, to a significance level of 0.05%.
RESULTS:
A total of 306 MBr and 124 NBr were enrolled. Mouth breathers were more likely to be male (p = 0.0002), have more frequent and more severe nasal obstruction and larger tonsils (p = 0.0001) than NBr. Mouth breathers also exhibited higher incidence rates of allergic rhinitis (p = 0.0001), of thoracic respiratory pattern (p = 0.0001), high-arched palate (p = 0.0001) and unfavorable postural classifications (p = 0.0001) with relation to the control group. Postural classification scores were directly proportional to nasal obstruction (p = 0.0001) and male sex (p = 0.0008).
CONCLUSIONS:
Postural problems were significantly more common among children in the group with mouth breathing syndrome, highlighting the need for early interdisciplinary treatment of this syndrome.

J Pediatr (Rio J). 2008 Nov-Dec;84(6):529-35.
Etiology, clinical manifestations and concurrent findings in mouth-breathing children.
[Article in English, Portuguese]
Abreu RR, Rocha RL, Lamounier JA, Guerra AF.
OBJECTIVE:
To investigate the etiology, main clinical manifestations and other concurrent findings in mouth-breathing children aged 3 to 9 years and resident in the urban area of Abaeté (MG), Brazil.
METHODS:
This study was based on a representative random sample of the town population, of 23,596 inhabitants. Clinical diagnosis of mouth-breathing was defined as a combination of snoring, sleeping with mouth open, drooling on the pillow and frequent or intermittent nasal obstruction. Children with a clinical diagnosis of mouth-breathing underwent nasal endoscopy, allergy skin tests and X ray of the rhinopharynx, full blood tests, eosinophil counts, total IgE assay and fecal parasitology. Data were analyzed using SPSS version 10.5.
RESULTS:
The main causes of mouth-breathing were: allergic rhinitis (81.4%), enlarged adenoids (79.2%), enlarged tonsils (12.6%), and obstructive deviation of the nasal septum (1.0%). The main clinical manifestations of mouth breathers were: sleeping with mouth open (86%), snoring (79%), itchy nose (77%), drooling on the pillow (62%), nocturnal sleep problems or agitated sleep (62%), nasal obstruction (49%), and irritability during the day (43%).
CONCLUSION:
Certain clinical manifestations are very common among mouth-breathing children. These manifestations must be recognized and considered in the clinical diagnosis of mouth-breathing.

Laryngoscope. 2010 Oct;120(10):2089-93.
The effect of mouth breathing versus nasal breathing on dentofacial and craniofacial development in orthodontic patients.
Harari D, Redlich M, Miri S, Hamud T, Gross M.
OBJECTIVES/HYPOTHESIS:
To determine the effect of mouth breathing during childhood on craniofacial and dentofacial development compared to nasal breathing in malocclusion patients treated in the orthodontic clinic.
STUDY DESIGN:
Retrospective study in a tertiary medical center.
METHODS:
Clinical variables and cephalometric parameters of 116 pediatric patients who had undergone orthodontic treatment were reviewed. The study group included 55 pediatric patients who suffered from symptoms and signs of nasal obstruction, and the control group included 61 patients who were normal nasal breathers.
RESULTS:
Mouth breathers demonstrated considerable backward and downward rotation of the mandible, increased overjet, increase in the mandible plane angle, a higher palatal plane, and narrowing of both upper and lower arches at the level of canines and first molars compared to the nasal breathers group. The prevalence of a posterior cross bite was significantly more frequent in the mouth breathers group (49%) than nose breathers (26%), (P = .006). Abnormal lip-to-tongue anterior oral seal was significantly more frequent in the mouth breathers group (56%) than in the nose breathers group (30%) (P = .05).
CONCLUSIONS:
Naso-respiratory obstruction with mouth breathing during critical growth periods in children has a higher tendency for clockwise rotation of the growing mandible, with a disproportionate increase in anterior lower vertical face height and decreased posterior facial height.

Arq Neuropsiquiatr. 2009 Sep;67(3B):860-5.
Mouth breathing children have cephalometric patterns similar to those of adult patients with obstructive sleep apnea syndrome.
Juliano ML, Machado MA, Carvalho LB, Prado LB, do Prado GF.
OBJECTIVE:
To determine whether mouth breathing children present the same cephalometric patterns as patients with obstructive sleep apnea syndrome (OSAS).
METHOD:
Cephalometric variables were traced and measured on vertical lateral cephalometric radiographs. The cephalometric measurements of 52 mouth and 90 nose breathing children were compared with apneic patients. The children had not undergone adenoidectomy or tonsillectomy and had not had or were not receiving orthodontic or orthopedic treatment.
RESULTS:
Mouth breathing children showed same cephalometric pattern observed in patients with OSAS: a tendency to have a retruded mandible (p=0.05), along with greater inclination of the mandibular and occlusal planes (p<0.01) and a tendency to have greater inclination of the upper incisors (p=0.08). The nasopharyngeal and posterior airway spaces were greatly reduced in mouth breathing children, as observed in patients with apnea (p<0.01).
CONCLUSION:
Mouth breathing children present abnormal cephalometric parameters and their craniofacial morphology resembles that of patients with OSAS.

Epilepsy Behav. 2008 Aug;13(2):284-9. Epub 2008 May 27.
Mouth breathing increases the pentylenetetrazole-induced seizure threshold in mice: a role for ATP-sensitive potassium channels.
Niaki SE, Shafaroodi H, Ghasemi M, Shakiba B, Fakhimi A, Dehpour AR.
Nasal obstruction and consequent mouth breathing have been shown to change the acid-base balance, producing respiratory acidosis. Additionally, there exists a large body of evidence maintaining that acidosis affects the activity of ATP-sensitive potassium (K(ATP)) channels, which play a crucial role in the function of the central nervous system (CNS), for example, in modulating seizure threshold. Thus, in the study described here, we examined whether mouth breathing, induced by surgical ligation of nostrils, could affect the seizure threshold induced by pentylenetetrazole in male NMRI mice. Using the selective K(ATP) channel opener (diazoxide) and blocker (glibenclamide), we also evaluated the possible role of K(ATP) channels in this process. Our data revealed that seizure threshold was increased 6 to 72 hours after nasal obstruction, reaching a peak 48 hours afterward, compared with either control or sham-operated mice (P<0.01). There was a significant decrease in pH of arterial blood samples and increase in CO(2) partial pressure (PCO(2)) during this time. Systemic injection of glibenclamide (1 and 2mg/kg, ip, daily) significantly prevented the increase in seizure threshold in 48-hour bilaterally nasally obstructed mice, whereas it had no effect on seizure threshold in sham-operated mice. Systemic injection of diazoxide (25mg/kg, ip, daily) had no effect on seizure threshold in all groups, whereas higher doses (50 and 100mg/kg, ip, daily) significantly increased seizure threshold in both 48-hour-obstructed and sham-operated mice. The decrease in seizure threshold induced by glibenclamide (2mg/kg, ip, daily) was prevented by diazoxide (25mg/kg, ip, daily). These results demonstrate for the first time that mouth breathing, which could result in respiratory acidosis, increases seizure threshold in mice and K(ATP) channels may play a role in this effect.

Respirology. 2008 Jun;13(4):553-8.
Enforced mouth breathing decreases lung function in mild asthmatics.
Hallani M, Wheatley JR, Amis TC.
BACKGROUND AND OBJECTIVE:
Nasal breathing provides a protective influence against exercise-induced asthma. We hypothesized that enforced oral breathing in resting mild asthmatic subjects may lead to a reduction in lung function.
METHODS:
Asymptomatic resting mild asthmatic volunteers (n = 8 ) were instructed to breathe either nasally only (N; tape over lips) or orally only (O; nose clip) for 1 h each, on separate days. Lung function (% predicted FEV(1)) was measured using standard spirometry at baseline and every 10 min for 1 h. ‘Difficulty in breathing’ was rated using a Borg scale at the conclusion of the N and O periods.
RESULTS:
Baseline FEV(1) on the N (101.2 +/- 3.8% predicted) and O (102.7 +/- 3.9% predicted) days was not significantly different (P > 0.3). At 60 min, FEV(1) on the O day (96.5 +/- 4.1% predicted) was significantly less than on the N day (101.0 +/- 3.5% predicted; P < 0.009). On the N day, FEV(1) did not change with time (P > 0.3), whereas on the O day, FEV(1) fell progressively (slope = -0.06 +/- 0.01% FEV(1)/min, P < 0.0001; linear mixed effects modelling). Three subjects experienced coughing/wheezing at the end of the O day but none experienced symptoms at the end of the N day. Subjects perceived more 'difficulty breathing in' at the end of the O day (1.5 +/- 0.4 arbitrary units) than on the N day (0.4 +/- 0.3 arbitrary unit; P < 0.05). CONCLUSIONS: Enforced oral breathing causes a decrease in lung function in mild asthmatic subjects at rest, initiating asthma symptoms in some. Oral breathing may play a role in the pathogenesis of acute asthma exacerbations.

Chest. 1999 Dec;116(6):1646-52.
Route of breathing in patients with asthma.
Kairaitis K, Garlick SR, Wheatley JR, Amis TC.
STUDY OBJECTIVES:
To measure route of breathing in chronic asthmatic patients during and after an acute severe exacerbation.
PATIENTS OR PARTICIPANTS:
Thirteen asthmatic patients were studied during hospital admission for acute asthma and, in 9 patients, again when asymptomatic. Nine healthy subjects were also studied.
INTERVENTIONS:
Spontaneous route of breathing was qualitatively assessed using oral and nasal thermistor probes, and was then quantified using a dual compartment face mask with attached pneumotachographs.
MEASUREMENTS AND RESULTS:
All asthmatic patients had severe bronchoconstriction initially (FEV(1), 46 +/- 3% of predicted) that had resolved at follow-up (FEV(1), 91 +/- 6% of predicted). No healthy subject had evidence of bronchoconstriction (FEV(1), 102 +/- 5% of predicted). During acute asthma, 11 asthmatics were spontaneously breathing oronasally, as assessed using thermistor probes, while all 13 breathed oronasally via face mask. When assessed using thermistor probes, seven of nine asymptomatic asthmatic patients studied were breathing exclusively via the nose; however, all breathed oronasally via face mask. In contrast, while eight of nine healthy subjects were also breathing exclusively via the nose when assessed using thermistor probes, all breathed nasally only via face mask.
CONCLUSIONS:
Thus, when asymptomatic and at rest, asthmatic patients breathe exclusively via the nose. However, during acute exacerbations of asthma, these patients switch to oronasal breathing. Unlike healthy subjects, chronic asthmatic patients also switch to oronasal breathing when wearing a face mask, irrespective of the degree of bronchoconstriction. We speculate that asthmatics may have an increased tendency to switch to oral breathing, a factor that may contribute to the pathogenesis of their asthma.

Int J Pediatr Otorhinolaryngol. 2009 Feb;73(2):227-36. Epub 2008 Dec 3.
Orientation and position of head posture, scapula and thoracic spine in mouth-breathing children.
Neiva PD, Kirkwood RN, Godinho R.
OBJECTIVE:
Mouth-breathing is a common clinical condition among school-age children and some studies have correlated this condition with quality of life and postural alterations. Therefore, the objective of this study was to investigate the orientation and position of the scapula, thoracic spine and head posture among mouth-breathing (MB) children and nasal-breathing (NB) children.
METHODS:
Twenty-one male MB children and 21 male NB children between 8 and 12 years of age participated in the study. Data were obtained through a stereophotogrammetry system that uses passive markers over anatomical landmarks to capture the position of the segments. Internal rotation, upward rotation, anterior tilt, scapular elevation and abduction were measured bilaterally as well as thoracic kyphosis, forward head position and shoulder protrusion.
RESULTS:
The MB children showed increased scapular superior position in relation to the NB group. No statistically significant differences were found between groups regarding the angular and linear measurements of the scapula. To verify reliability, three measurements were taken for each variable in the study. The intraclass correlation coefficient (ICC) showed results above 0.8 for all the variables except for the internal rotation angle (I-Rot), below 0.5, probably due to uncertainty in the palpation of the inferior angle of the scapula. Ninety-five percent of the NB children and 58% among the MB children had been breastfed, this difference was statistically significant. There were statistically significant differences between groups regarding the domains of the Autoquestionnaire Qualité de Vie Enfant Imagé (AUQEI) scale and body mass index, which was higher among the NB children.
CONCLUSIONS:
MB children increased scapular superior position in comparison to NB children due probably to the position of forward head, leading to an alteration in the positioning of the mandible. The absence of significantly difference in posture pattern between groups in the present study could attributed to height-weight development in this age, as the posture of children changes in order to adapt to new body proportions, regardless of health status. The results observed in this study demonstrate the importance of using reliable measurements in the postural assessment of MB and NB children helping physical therapists to focus their strategies during rehabilitation in more specific conditions.

J Pediatr (Rio J). 2008 Mar-Apr;84(2):171-7.
The relationship between excursion of the diaphragm and curvatures of the spinal column in mouth breathing children.
Yi LC, Jardim JR, Inoue DP, Pignatari SS.
OBJECTIVE:
To investigate the relationship between excursion of the diaphragm muscle and spinal curvatures in mouth breathing children.
METHODS:
A total of 52 children of both sexes, aged from 5 to 12 years, were studied. After otorhinolaryngological assessment, the children were divided into two groups: mouth breathers and nose breathers. All of the children underwent videofluoroscopic examination of the diaphragm muscle and postural assessment. Diaphragm excursion was analyzed using Adobe Photoshop software, and postural assessment was recorded using photographs in left lateral view, which were then analyzed using SAPO postural assessment software.
RESULTS:
The groups studied exhibited statistically significant differences in terms of spinal curvatures (cervical lordosis: p = 0.003; lumbar lordosis: p = 0.001; thoracic kyphosis: p = 0.002; position of the pelvis: p = 0.001) and diaphragm excursion (right side diaphragm: p = 0.001; left side diaphragm: p = 0.001). The mouth breathing group exhibited reduced cervical lordosis, increased thoracic kyphosis, increased lumbar lordosis and the position of the pelvis was tilted forward. The distance traveled outwards by the diaphragm muscles of mouth breathing children was shorter than that traveled by the muscles of nose breathing children. The relationship between the behavior of spinal curvatures and diaphragm excursion had no statistical significance.
CONCLUSION:
There was no relationship between spinal curvatures and diaphragm excursion in the groups studied here.

Pro Fono. 2007 Oct-Dec;19(4):347-51.
[Characteristics of the stomatognathic system of mouth breathing children: anthroposcopic approach].
[Article in Portuguese]
Cattoni DM, Fernandes FD, Di Francesco RC, Latorre Mdo R.
BACKGROUND:
the use of anthroposcopy in the assessment of posture and morphology of the stomatognathic system of mouth breathing children.
AIM:
to describe the postural and morphologic characteristics of the stomatognathic system of mouth breathing children, according to age.
METHOD:
participants were 100 children, of both genders, with ages ranging from 7 to 11 years and 11 months, leukoderms, in mixed dentition and with the diagnosis of mouth breathing. The investigated postural and morphologic characteristics of the stomatognathic system were labial and lingual resting position, possibility of labial occlusion, hyperfunction of the mentalis muscle during labial occlusion, bite and morphology of the lower lip, cheeks and hard palate, using the anthroposcopy methodology.
RESULTS:
the results referring to the characterization of the studied population, according to the most frequent otorhinolaryngologic diagnosis, was of enlarged pharyngeal and palatine tonsils. A statistically significant difference was found between the percentages of each otorhinolaryngologic diagnosis, according to age. The results of the characteristics of the stomatognathic system indicated that the most common aspects in the studied sample were: half-open lips when in the resting position, tongue lowered on the mouth’s floor in the resting position, possibility of labial occlusion, hyperfunction of the mentalis muscle during labial occlusion, alterations of bite, labioverted, symmetry of the cheeks and alteration of the hard palate. All of the studied characteristics presented the same frequency with the increase in age, with no statistically significant difference.
CONCLUSION:
mouth breathing children presented pathologic adaptations in the postural and morphological characteristics of the stomatognathic system. This suggests the importance of early diagnosis in order to avoid orofacial alterations.

Aust J Sci Med Sport. 1995 Sep;27(3):51-5.
Comparison of maximal oxygen consumption with oral and nasal breathing.
Morton AR, King K, Papalia S, Goodman C, Turley KR, Wilmore JH.
The major cause of exercise-induced asthma (EIA) is thought to be the drying and cooling of the airways during the ‘conditioning’ of the inspired air. Nasal breathing increases the respiratory system’s ability to warm and humidity the inspired air compared to oral breathing and reduces the drying and cooling effects of the increased ventilation during exercise. This will reduce the severity of EIA provoked by a given intensity and duration of exercise. The purpose of the study was to determine the exercise intensity (%VO2 max) at which healthy subjects, free from respiratory disease, could perform while breathing through the nose-only and to compare this with mouth-only and mouth plus nose breathing. Twenty subjects (11 males and 9 females) ranging from 18-55 years acted as subjects in this study. They were all non-smokers and non-asthmatic. At the time of the study, all subjects were involved in regular physical activity and were classified, by a physician, as free from nasal polyps or other nasal obstruction. The percentage decrease in maximal ventilation with nose-only breathing compare to mouth and mouth plus nose breathing was three times the percentage decrease in maximal oxygen consumption. The pattern of nose-only breathing at maximal work showed a small reduction in tidal volume and large reduction in breathing frequency. Nasal breathing resulted in a reduction in FEO2 and an increase in FECO2. While breathing through the nose-only, all subjects could attain a work intensity great enough to produce an aerobic training effect (based on heart rate and percentage of VO2 max).

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Calorie Restriction, PUFA, and Aging

Also see:
Protect the Mitochondria
PUFA Accumulation & Aging
Unsaturated Fats and Longevity
Anti-Inflammatory Omega -9 Mead Acid (Eicosapentaenoic acid)
Protective “Essential Fatty Acid Deficiency”
“Curing” a High Metabolic Rate with Unsaturated Fats
Fat Deficient Animals – Activity of Cytochrome Oxidase
Dietary PUFA Reflect in Human Subcutaneous Fat Tissue
Toxicity of Stored PUFA
PUFA, Development, and Allergy Incidence
PUFA, Aging, Cytochrome Oxidase, and Cardiolipin

Quotes by Ray Peat, PhD:
“Calorie-restricted animals (on a diet of normal composition) have a lower degree of fat unsaturation in their mitochondria as they age, preserving the relatively more saturated fats of youth.”

“In this culture that repeatedly makes such claims of essentiality, the growing number of reports of biological superiority of “deficient” animals suggests that nutritional research may be near the point at which it can resume the line of study begun by Northrup, Osborne, Mendel, Drummond, Bernstein, Elias, and others, that was interrupted for 60 years by industrial interests that promoted antiscientific opinions.

For example, in 1914 F.P. Rous showed that limiting food intake reduced the incidence of cancer, and then in 1915 and 1917, Osborne and Mendel showed that food restriction extended the fertility and longevity of female rats. The association between estrogen and cancer had become known during this time, and vitamin E, which was originally known as the fertility vitamin, was soon recognized to have antiestrogenic properties, as well as to prevent the deadly effects of excessive polyunsaturated fats in the diet. My endocrinology professor, A.S. Soderwall, who had found that excess estrogen prevented (or interrupted) pregnancy, demonstrated that increased vitamin E extended fertility in aging female rodents.

By the time I began my research, it seemed clear that it had been the reduction of PUFA in the diet which, like the addition of vitamin E, had prevented sterility in the calorie restriction experiments, and that those treatments had limited the effects of estrogen in the aging organisms.”

“Caloric restriction does extend the life span of many species, but it generally preserves the high metabolic rate of youth, so that at a given age the calorie-restricted animal has a higher rate of oxygen consumption per gram of body weight than the unrestricted eaters”

Mech Ageing Dev. 2005 Sep;126(9):1003-10.
Membrane alteration as a basis of aging and the protective effects of calorie restriction.
Yu BP.
As has been experimentally determined, oxidative modification to biological systems can be extensive, although the identification and stochiometric relation of the reactive species that cause these alterations have not been fully elucidated. In this review, arguments are presented to support the notion that the combined effects of membrane lipid peroxidation and its by-products, reactive aldehydes are likely responsible for membrane-associated functional declines during aging. As evidence for a systemic response to overall oxidative stress, the molecular inflammation hypothesis of aging is discussed by considering that the activation of inflammatory genes act as a bridge linking normal aging to pathological processes.

The phospholipids of mitochondria and microsomes become more unsaturated with aging (Laganiere and Yu, 1993, Lee, et al., 1999). -Ray Peat, PhD

Gerontology. 1993;39(1):7-18.
Modulation of membrane phospholipid fatty acid composition by age and food restriction.
Laganiere S, Yu BP.
Phospholipids from liver mitochondrial and microsomal membrane preparations were analyzed to further assess the effects of age and lifelong calorie restriction on membrane lipid composition. Results showed that the major phospholipid classes, phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol and cardiolipin did not vary significantly with age or diet. The fatty acid composition of the phospholipids was determined in PC and PE and ages of 6, 12 and 24 months. The data revealed characteristic patterns of age-related changes in ad libitum (AL) fed rats: membrane levels of long-chain polyunsaturated fatty acids, 22:4 and 22:5, increased progressively, while membrane linoleic acid (18:2) decreased steadily with age. Levels of 18:2 fell by approximately 40%, and 22:5 content almost doubled making the peroxidizability index increase with age. In addition, levels of 16:1 and 18:1 decreased significantly with age, indicating a possible change in delta 9-desaturase activity coefficient. Food restriction resulted in a significant increase in levels of essential fatty acids while attenuating levels of 22:4, 22:5, 22:6 and peroxidizability. We concluded that the membrane-stabilizing action of long-term calorie restriction relates to the selective modification of membrane long-chain polyunsaturated fatty acids during aging.

Free Radic Biol Med. 1999 Feb;26(3-4):260-5.
Modulation of cardiac mitochondrial membrane fluidity by age and calorie intake.
Lee J, Yu BP, Herlihy JT.
The aim of the present study was to determine the effects of dietary restriction (DR) on the age-related changes in membrane fluidity, fatty acid composition and free radical damage of mitochondrial membranes obtained from the rat left ventricle. Mitochondrial membrane preparations were obtained from the left ventricles of 6- and 24-month-old, male, Fischer 344 rats that were allowed to eat throughout their life either ad lib (Group A) or only 60% of the amount consumed by the ad lib fed group (Group B). Our results show that the membrane fluidity of the 24 month Group A hearts was less than that of the 6 month group A hearts. No differences in membrane fluidity were observed between the 6 and 24 month DR groups. The fatty acid composition of the mitochondrial membranes of the two ad lib fed groups differed: the long-chain polyunsaturated 22:4 fatty acid was higher in the older group, although linoleic acid (18:2) was lower. DR eliminated the differences. No statistically significant difference in the overall polyunsaturated fatty acid content was noted. However, the peroxidizability index was higher in the membranes of the 24 month Group A hearts but not in the 24 month Group B hearts. Finally, the degree of lipid damage, as assessed in vitro by the induced production of reactive oxygen species, was elevated in the 24 month Group A hearts. No difference was observed between the young and old DR groups. Considered together, these results suggest that DR maintains the integrity of the cardiac mitochondrial membrane fluidity by minimizing membrane damage through modulation of membrane fatty acid profile.

Biochem Biophys Res Commun. 1987 Jun 30;145(3):1185-91.
Anti-lipoperoxidation action of food restriction.
Laganiere S, Yu BP.
Chronic food restriction inhibited the age-related increase of malondialdehyde production and lipid hydroperoxides in liver mitochondrial and microsomal membranes of ad libitum fed Fischer 344 rats. The anti-lipoperoxidation action of food restriction could not be attributable to the changes in membrane lipid content nor vitamin E status. Restricting calories modified membrane fatty acid composition by increasing linoleic acid and decreasing docosapentaenoic acid content in both membranes. The significance of the fatty acid modification was discussed in terms of anti-lipoperoxidation and membrane fluidity.

Aging Clin Exp Res. 2004 Dec;16(6):425-31.
Effects of dietary restriction on age-related changes in the phospholipid fatty acid composition of various rat tissues.
Tamburini I, Quartacci MF, Izzo R, Bergamini E.
BACKGROUND AND AIMS:
Polyunsaturated fatty acids (PUFAs) are essential components of the cell lipid bilayer and are involved in membrane fluidity and normal functioning, but they are vulnerable to free radical attack. Given the role of oxidative stress in the aging process, age-related changes in phospholipid fatty acid (PLFA) composition in rat liver, kidney and heart were assessed in 3-, 12- and 24-month-old rats fed either ad libitum but only every other day, or daily but only 60% of the quantity normally consumed by age-matched controls.
METHODS:
Lipids were extracted and phospholipids (PLs) were separated using the solid phase extraction technique, then transesterified and assayed by gas-liquid chromatography.
RESULTS:
Saturated fatty acids (FAs) did not change significantly with age; mono- and bi-unsaturated FAs decreased in the liver and heart, and the ratio of the former to the latter increased in the liver, kidney and heart. PUFAs increased in the liver and heart. As regards individual FAs, 20:1(n-9) decreased in all organs, 14:1 and 18:1(n-7) increased in the kidney and heart, 18:1(n-9) increased in the kidney, 20:2(n-6), 18:2(n-6) and 22:5(n-3) decreased in the liver and heart, 20:3(n-6) decreased in the kidney and increased in the heart. The most abundant PUFAs, 20:4(n-6) and 22:6(n-3), either remained the same or increased with age. The N-9 family increased in the kidney, the N-7 family increased in the kidney and heart, the N-6 family decreased in all three organs, and the N-3 family increased in the liver and kidney. Dietary restriction (DR) significantly counteracted most of these changes, but changes in some FAs [20:2(n-6) in the heart] were magnified by DR and may not be age-related.
CONCLUSIONS:
Most age-related changes (that occurred in the rat liver, kidney and heart and were counteracted by the two different types of DR) may be involved in the mechanism of aging.

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