Fermentable carbohydrates: A link between periodontal disease and cardiovascular disease?

The first paper to indicate a link between dental disease and heart disease was wrote by Cleave and Campbell in 1966. In their article these researchers have postulated that excessive fermentable carbohydrates could led to both dental and systemic diseases (1). Yudkin, sharing the same opinion from Cleave, wrote in 1972: “My research on coronary heart disease has convinced me beyond doubt that sugar plays a considerable part in this terrifying epidemic” (2). While both Cleave and Yudkin had distinct hypotheses regarding which dietary carbohydrates caused chronic non-communicable diseases (CNCDs), they were unified regarding the significance of high-glycemic dietary carbohydrates and dental CNCDs. According to Cleave-Yudkin’s hypothesis—both dental and systemic CNCDs were due to an excess intake of fermentable carbohydrates, dental CNCDs were the early marker for systemic CNCDs, and dental CNCDs should be primarily prevented by restriction of fermentable carbohydrates.
Hujoel, in an excellent review paper published in 2009 (3) told that:
“In favor of Cleave-Yudkin’s hypothesis is the ability to predict and explain dental-systemic disease associations that were unknown when the hypothesis was formulated. It is now known, for instance, that markers of abnormal glucose metabolism, such as high levels of advanced glycation end-products or post-load plasma glucose concentration, have been related to diverse systemic outcomes such cardiovascular disease (Jandeleit-Dahm and Cooper, 2008). Similarly, the more a diet drops dental plaque pH, the more it spikes blood glucose levels, providing an elegant biological plausibility model for Cleave-Yudkin’s hypothesis that dental caries is an alarm bell for systemic CNCDs (Lingström et al., 1993)”.
Confirming the Cleave-Yudkin’s hypothesis an Italian study published last week has shown that high dietary glycemic load and carbohydrate intake from high-GI foods increase the overall risk of cardiovascular disease in women, but not in men. In practice the study shows that women who eat more white bread, white rice, pizza, and other carbohydrate-rich foods, that cause blood sugar to spike, are more than twice as likely to develop heart disease than women who eat less of those foods. This study involving 47 749 volunteers (15 171 men and 32 578 women), who completed a dietary questionnaire, had a median duration of 7.9 years of follow-up with 463 CHD cases (158 women and 305 men) identified. The authors said in their paper that a possible reason for the failure to find an association between a high glycemic diet and CHD among men could be that adverse changes in plasma HDL cholesterol and triglyceride levels, as a result of a high glycemic diet, are stronger risk factors for CVD in women than men (4).
It is interesting to notice that high-carbohydrate diets, particularly in the form of high-glycemic index carbohydrate, may keep the sympathetic nervous system overactive (5). Also that high carbohydrate diet may increase significantly the activity of serum lactate dehydrogenase (6).
All the points cited above supply evidences for our acidity theory of atherosclerosis (6).
Treatment of periodontal disease in prevention of atherosclerosis
Some recent studies have shown that treatment of periodontal disease results in benefits for the prevention of atherosclerosis. Tonetti and colleagues have shown that intensive periodontal treatment, 6 months after therapy, the benefits in oral health were associated with improvement in endothelial function (7). Piconi et al have confirmed that treatment of periodontal disease results in improvements of endothelial dysfunction, aside a reduction of the carotid intima-media thickness. The authors of this paper have concluded that these results offer further support to the hypothesis that periodontal disease predisposes to atherosclerosis, shedding some light on the mechanisms possibly associated with this hypothesis, and reinforce the idea that atherosclerosis is an immune-mediated disease (8).
An alternative hypothesis
Taking in view that some risk factors like smoking habits, stress, genetics, increasing age and high-carbohydrates diets contribute to both periodontitis and cardiovascular disease we have an alternative hypothesis through the following mechanisms:
- A street with double directions for driving -
1) From one side the transport from the mouth directly to the blood circulation, through the sublingual route, of sugars related to high-carbohydrate diets leading to an overactive sympathetic nervous system and then to the atherosclerotic process. This idea is based in the regular use of the sublingual route with diffusion directly in the venous circulation for fast effects of remedies including cardiovascular drugs.
2) On the other side the saliva concentrations representing a mix of local chronic inflammatory response plus the acidity of other body conditions derived mostly from chronic stress aside from other factors expressed by markers of blood acidity, lactate dehydrogenase activity, sympathetic nervous system activity and hypothalamic-pituitary-adrenal activity. In our view this second road may also contribute to dental disease.
Carlos Monteiro
1. Cleave TL, Campbell GD (1966). Diabetes, coronary thrombosis, and the saccharine disease Bristol,: Wright
2. Yudkin J (1972b). Sweet and dangerous; the new facts about the sugar you eat as a cause of heart disease, diabetes, and other killers. New York: P.H. Wyden, Inc.
3. Hujoel P, Dietary Carbohydrates and Dental-Systemic Diseases, J Dent Res 2009; 88; 490. Abstract at http://jdr.sagepub.com/cgi/content/abstract/88/6/490
4. Sabina Sieri,Vittorio Krogh, et al . Dietary Glycemic Load and Index and Risk of Coronary Heart Disease in a Large Italian Cohort, EPICOR Study. Arch Intern Med. 2010;170(7):640-647
5. Koop W. Chronically increased activity of the sympathetic nervous system: our diet-related “evolutionary” inheritance. The Journal of Nutrition, Health & Aging Volume 13, Number 1, 2009
6. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
7. Tonetti MS et al. Treatment of Periodontitis and Endothelial Function, NEJM - Volume 356:911-920, March 1, 2007
8. Piconi S et al.Treatment of periodontal disease results in improvements in endothelial dysfunction and reduction of the carotid intima-media thickness. FASEB J. 23, 1196–1204 (2009)

The link between air pollution and atherosclerosis: What is the right biological explanation?

Studies around the world have consistently shown that both short and long term exposures to Particulate Matter (PM) air pollution are associated with a host of cardiovascular diseases, including myocardial ischemia and infarctions, heart failure, arrhythmias, strokes and increased cardiovascular mortality.
Very recently it was published a study in humans confirming the association of the exposure to ambient air pollution and atherosclerosis through the progression of carotid artery intima-media thickness (1).
In an interesting recent paper by Robert Brook (2) he states that there are three putative ‘general’ pathways to explain the biological mechanisms whereby PM exposure may be capable of mediating cardiovascular events: 1) autonomic mechanisms: parasympathetic nervous system withdraw and/or sympathetic nervous system activation; 2) the release of circulating pro-oxidative and/or pro-inflammatory mediators from the lungs (e. g. cytokines and activated immune cells) into the systemic circulation following PM inhalation that, in turn, indirectly mediate CV responses; and; 3) nano-scale particles and/or soluble PM constituents translocating into the systemic circulation after inhalation that then directly interact with the CV system. According to Robert Brook, chronic actions of PM and the enhancement of atherosclerosis, are most likely to be induced by the generation of a chronic pro-inflammatory state (pathway 2).
Taking in view the results of studies in humans showing that particulate air pollutants continuous exposition decreases the heart rate variability (3,4) and may lead to an impaired autonomic control with potential acceleration in the progression of atherosclerosis (5,6,7), with the due respect, I feel obliged to differ from Brook’s opinion regarding the biological mechanism related to chronic PM exposure and atherosclerosis.
In our view the sympathetic over activity may start the whole process of atherosclerosis which ends in the inflammatory state as hypothesized in the acidity theory of atherosclerosis (8) and discussed in our last article in this blog (9)
Carlos Monteiro
1. Nino Kunzli, Michael Jerrett, Raquel Garcia-Esteban, Xavier Basagana, Bernardo Beckermann, Frank Gilliland, Merce Medina, John Peters, Howard N. Hodis, Wendy J. Mack. "Ambient Air Pollution and the Progression of Atherosclerosis in Adults." PloS ONE 5(2): e9096. doi:10.1371/journal.pone.0009096, February 8, 2010. Full free text at http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.00090962. Brook RD, Cardiovascular effects of air pollution. Clinical Science (2008) 115, (175–187) Full free text at http://www.clinsci.org/cs/115/0175/1150175.pdf
3. Duanping Liao, Yinkang Duan, Eric A. Whitsel, Zhi-jie Zheng, Gerardo Heiss, Vernon M. Chinchilli, and Hung-Mo Lin. Association of Higher Levels of Ambient Criteria Pollutants with Impaired Cardiac Autonomic Control: A Population-based Study, Am J Epidemiol 2004;159:768–777
4. C. Arden Pope III, Matthew L. Hansen, Russell W. Long, Karen R. Nielsen, Norman L. Eatough, William E. Wilson, and Delbert J. Eatough. Ambient Particulate Air Pollution, Heart Rate Variability, and Blood Markers of Inflammation in a Panel of Elderly Subjects. Environmental Health Perspectives, V 112; N 3: March 2004
5. Heikki V. Huikuri; Vesa Jokinen; Mikko Syvänne; Markku S. Nieminen; K. E. Juhani et al, Heart Rate Variability and Progression of Coronary Atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:1979-1985.
6. Anders Gottsäter , Åsa Rydén Ahlgren, Soumia Taimour and Göran Sundkvist, Decreased heart rate variability may predict the progression of carotid atherosclerosis in type 2 diabetes Clinical Autonomic Research Volume 16, Number 3 / June, 2006
7. J. C. Longenecker, M. Zubaid, K.V. Johny, A.I. Attia, J. Ali, W. Rashed, C.G. Suresh, M. Omar. Association of low heart rate variability with atherosclerotic cardiovascular disease in hemodialysis patients. Med Princ Pract 2009;18:85-92
8. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
9. Sympathetic predominance: a primary factor in the cascade of events leading to the atherogenic spiraling, Carlos Monteiro, Monday, February 22, 2010 at http://aciditytheory.blogspot.com/2010/02/sympathetic-predominance-primary-factor.html

Sympathetic predominance: a primary factor in the cascade of events leading to the atherogenic spiraling.

Sympathetic overactivity has been found to be associated with blood pressure and lipid abnormalities (1,2,3). In this respect a recent study has demonstrated that sympathetic overactivity may favour the development of sustained hypertension and hypercholesterolemia early in life, and lead to increased susceptibility of vascular complications. (4).
In fact accumulating data collected in animals and humans suggest that metabolic syndrome is associated with markers of adrenergic overdrive. Several markers of adrenergic drive, such as plasma norepinephrine, norepinephrine spillover from adrenergic nerve terminals, heart rate and others, have all show an increase in the different conditions clustering in metabolic syndrome like obesity, hypertension and insulin resistance state (5,6). Evidence also has shown that the sympathetic activation participates in the development of hypertension-related target organ damage, such as left ventricular diastolic dysfunction (7).
It is well established that the sympathetic nervous system (SNS) activity is also influenced by food ingestion, and that diet composition plays an important role. What is interesting to note is that, among dietary types, carbohydrates (starch and sugars) ingestion significantly increases SNS activity, especially in high-glycemic load, with deleterious effects to human health (8). On the other side protein or fat ingestion have no significant sympathoexcitatory effect (9,10,11).
The evidences above mentioned strengthen our views regarding to the acidity theory of atherosclerosis where continuous stress is placed as the most important risk factor (12). However, this do not undermine the value of other key factors as expressed in our monography:
“The acidity theory of atherosclerosis does not underestimate the importance of other key factors for atherosclerosis like ageing, improper diet, environmental pollution, lifestyle, physical inactivity, tobacco smoking and genetic predisposition. However, most of these risk factors might result in altered autonomic nervous system, sympathetic bias, increased lactic acid and acidic environment thus propitiating atherogenesis. Our proposal may extend to any respiratory or metabolic disturbances resulting in acidosis.“
Carlos Monteiro
1. Masuo K, Mikami H, Ogihara T, Tuck ML. Sympathetic nerve hyperactivity precedes hyperinsulinemia and blood pressure elevation in a young, nonobese Japanese population. Am J Hypertens 1997; 10:77–83.
2. Nakao M, Nomura K, Karita K, Nishikitani M, Yano E. Relationship between brachial-ankle pulse wave velocity and heart rate variability in young Japanese men. Hypertens Res 2004; 27:925–931.
3. Arner P, Wahrenberg H, Lonnqvist F, Angelin B. Adipocyte betaadrenoceptor sensitivity influences plasma lipid levels. Arterioscler Thromb Vasc Biol 1993; 13:967–972.
4. Palatini P, Longo D, Zaetta V, Perkovic D, Garbelotto R and Pessina AC. Evolution of blood pressure and cholesterol in stage 1 hypertension: role of autonomic nervous system activity. Journal of Hypertension 2006, 24:1375-1381
5. Mancia G, Bousquet P et al. The sympathetic nervous system and the metabolic syndrome. Journal of Hypertension 2007, 25 (5):909-920
6.Grassi G, Quarti-Trevano F et al. Cariovascular risk and adrenergic overdrive in metabolic syndrome. Nutr Metab Cardiovasc Dis 2007, 17(6): 473-81
7. Grassi G, Seravalle G et al. Sympathetic and baroreflex cardiovascular control in hypertension-related left ventricular dysfunction. Hypertension 2009;53:205-209. Full free paper at http://hyper.ahajournals.org/cgi/content/full/53/2/205
8. Koop W. Chronically increased activity of the sympathetic nervous system: our diet-related “evolutionary” inheritance. The Journal of Nutrition, Health & Aging Volume 13, Number 1, 2009
9. Welle S, Ulavivat U, Campell G. Thermic effect of feeding in men: Increased plasma
norepinephrine levels following glucose but not protein or fat consumption. Metabolism 1981; 30: 953-958
10. Welle SL, Lilavivathana U,Campell RG. Increased plasma nor epinephrine concentrations and metabolic rates following glucose ingestion in man. Metabolism 1980; 29: 806-09
11. Tentolouris N, Tsigos D, Perea E et al. Differential effect of high-fat and high carbohydrate isoenergetic meals on cardiac autonomic nervous system activity in
lean and obese women. Metabolism 2003; 52: 1426-32
12. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf

What causes the elevation of cholesterol levels in blood?

Follows some suggestions from medical literature about factors, beyond the famous but wronged and simplistic idea that foods based on saturated fats cause the development of atherosclerosis (1, 22, 23), suggesting that stress, high carbohydrate diets and smoke may raise total cholesterol and low density lipoproteins levels:
1. Stress
a) Anxiety and cholesterol elevation (2, 3, 4, 5, 6, 7, 8, 9, 10, 11)
b) Hostility and cholesterol elevation (12, 13, 14)
c) Extreme physical exertion and cholesterol elevation (15)
2) High carbohydrate diets and cholesterol elevation (16, 17, 18).
3) Smoke and cholesterol elevation (19, 20).
It is interesting to notice that specially in stress conditions and in high carbohydrate diets there is a significant elevation in blood lactic acid, with paralleling elevation of cholesterol levels in blood which represents in our view, a healing response of the body to the vascular endothelial lesion (21).
As Dr. Malcolm Kendrick, a colleague from the International Network of Cholesterol Skeptics (THINCS), use to say: "Do cigarettes contain fat? No, not at all. So, how can smoking a cigarette, containing no fat or cholesterol, end up depositing fat and cholesterol in the artery walls. What is the mechanism for that?"
By the way, in a recent paper the authors have assessed all dietary interventions using Dietary Cholesterol (DC) or eggs and presented their own conclusions. They point out that short-term effects where there is a rise in plasma cholesterol with DC should be interpreted with caution because they differ from long-term effects where there is no relationship between DC and plasma cholesterol (22).
Carlos Monteiro
Note:
A recent meta-analysis of prospective epidemiologic studies during 5–23 years of follow-up of 347,747 subjects showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD. Consideration of age, sex, and study quality did not changed the results (23)
1. Uffe Ravnskov, Cholesterol Myths at http://www.ravnskov.nu/cholesterol.htm
2) Changes in plasma lipids with psychosocial stress are related to hypertension status and the norepinephrine stress response. Wirtz PH, Ehlert U, Bärtschi C, Redwine LS, von Känel R. Metabolism. 2009 Jan;58(1):30-7.
3. Effects of hemoconcentration and sympathetic activation on serum lipid responses to brief mental stress, Elizabeth A. Bachen, Matthew F Muldoon et al, Psychosomatic Medicine 64:587-594 (2002)
4. Serum lipids, neuroendocrine and cardiovascular responses to stress in healthy Type A men, Fredrikson M, Blumenthal JA, Biol Psychol. 1992 Oct;34(1):45-58
5. Factors associated with the development of panic attack and panic disorder: survey in the Japanese population Kaiya H et al. Psychiatry Clin Neurosci. 2005 Apr;59(2):177-82a
6. Changes in mental well-being, blood pressure and total cholesterol levels during workplace reorganization: the impact of uncertainty, Taylor & Francis V15, N1 January 1, 2001: 14-18
7. Examination stress: changes in serum cholesterol, triglycerides and total lipids. Agarwal V, Gupta B, Singhal U, Bajpai SK. Indian J Physiol Pharmacol. 1997 Oct;41(4):404-8.
8. Wives of patients with acute myocardial infarction are at an increased risk of developing coronary artery disease, Papamichael Ch et al, J Cardiovasc Risk. 2002 Feb;9(1):49-52
9. Lipid reactivity to stress: I. Comparison of chronic and acute stress responses in middle-aged pilots, Stoney CM et al, Health Psychol. 1999 May;18(3):241-250
10. Associations between acute lipid stress responses and fasting lipid levels 3 years later, Andrew Steptoe and Lena Brydon, Health Psychology 2005, Vol. 24, No. 6, 601-607
11. Effect of preoperative stress on serum cholesterol level in humans. Sane AS, Kukreti SC, Experientia. 1978 Feb 15; 34(2): 213-4
12. Prevalence of hostility in young coronary artery disease patients and effects of cardiac rehabilitation and exercise training, Lavie CJ, Milani RV, Mayo Clin Proc. 2005 Mar;80(3):335-42
13.Richards JC, Hof A, Alvarenga M. Serum lipids and their relationships with hostility and angry affect and behaviors in men.Health Psychol. 2000 Jul;19(4):393-8.
14. Hostility-related differences in the associations between stress-induced physiological reactivity and lipid concentrations in young healthy women.Suarez EC, Harralson TL. Int J Behav Med. 1999;6(2):190-203.
15. Changes in lipoprotein profiles during intense military training. B. L. Smoak, J. P. Norton, E. W. Ferguson and P. A. Deuster. Journal of the American College of Nutrition, Vol 9, Issue 6 567-572
16. Metabolic effects of dietary fructose in healthy subjects.Swanson JE, Laine DC, Thomas W, Bantle JP. Am J Clin Nutrition 1992;55:851-6
17. Blood lipids, lipoproteins, apoproteins, and uric acid in men fed diets containing fructose or high-amylose cornstarch. Reiser S. Powell AS, Scholfield DI. Panda P. Ellwood KC. Canary II. Am J Clin Nutr 1989:49:832-9.
18. Hallfrisch J, Reiser 5, Prather ES. Blood lipid distribution of hyperinsulinemic men consuming three levels of fructose. Am J Clin Nutr 1983:37:740-8.
19. The Relationship Between Smoking, Cholesterol, and HDL-C Levels in Adult Women
Bert H. Jacobson; Steven G. Aldana; Troy B. Adams; Michael Quirk; Haworth, Women & Health, Volume 23, Issue 4 July 1996 , pages 27 - 38
20. Smoking and smoking cessation -- the relationship between cardiovascular disease and lipoprotein metabolism: a review. Chelland Campbell S, Moffatt RJ, Stamford BA. Atherosclerosis. 2008 Dec;201(2):225-35
21. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at
http://www.infarctcombat.org/AcidityTheory.pdf
22. Fernandez ML and Calle M. Revisiting Dietary Cholesterol Recommendations: Does the Evidence Support a Limit of 300 mg/d?, August 4, 2010
23. Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease, Patty W Siri-Tarino, Qi Sun, Frank B Hu, and Ronald M Krauss. Am J Clin Nutr doi: 10.3945/ajcn.2009.27725. First published ahead of print January 13, 2010

Psoriasis linked to atherosclerosis: An unsolved mystery?

During the last years several studies have reported that patients with psoriasis are more likely to have traditional cardiovascular risk factors, such as hyperlipidemia, hypertension, diabetes, obesity, tobacco use, and a history of previous myocardial infarction (1, 2).
Very recently a new study has suggested that psoriac patients have more propensity for coronary artery, cerebrovascular and peripheral vascular diseases resulting in increased mortality. This study compared rates of heart disease, stroke-related vascular disease and peripheral artery disease (PAD), and death among 3.236 people with psoriasis (mostly men between 50-60 years) and 2.500 people without this condition. Overall people with psoriasis were nearly twice as likely to have been diagnosed with heart disease, stroke related vascular disease or PAD. What’s more, 19.6% of people with psoriasis died during the study, compared with 9.9% of participants who did not have psoriasis (3).
In reality many recent studies are showing the prevalence of subclinical atherosclerosis in patients with psoriasis compared with health patients, through a marked increase in the carotid artery intima-media thickness, measured by ultrasonography (4,5,6 ,7,8).
Also, a study has shown that subclinical atherosclerosis in psoriac patients is significantly associated with increased sugar and triglyceride levels (6)
Other studies have shown that metabolic systems may be disturbed in association with psoriasis, with many compounds formed in excess from glucose, like lactic acid (9). It is interesting to notice that Boyd and Menter found that 13 (62%) of 21 patients with erythroderma, the most severe form of psoriasis, had elevated serum lactic deydrogenase (10). Another study have indicated a shift of enzymatic activity of lactate deydrogenase in erythrocyte in psoriasis towards LDH2 and LDH1, and thus to enhanced energy production by oxidation in psoriatic patients as compared with normal controls (11).
According to some researchers the mechanism by which premature atherosclerosis develops in psoriasis remains an unsolved mystery, becoming a focus of current research to further elucidate the pathophysiology underlying and connecting these two diseases (12).
Taking in view the above findings I think the acidity theory may offer a valid and potential pathophysiological mechanism to explain the link psoriasis/atherosclerosis (13)

1) Matthew Meier and Pranav B. Sheth, Clinical Spectrum and Severity of Psoriasis. Curr Probl Dermatol. Basel, Karger, 2009, vol 38, pp 1–20. Full free paper at http://www.online.karger.com/ProdukteDB/Katalogteile/isbn3_8055/_91/_51/CUPDE38_02.pdf
2) Mehta NN, Azfar RS, Shin DB, Neimann AL, Troxel AB, Gelfand JM. Patients with severe psoriasis are at increased risk of cardiovascular mortality: cohort study using the General Practice Research Database. Eur Heart J. 2009 Dec 27.
3) Prodanovich S, Kirsner RS, Kravetz JD, Ma F, Martinez L, Federman DG.. Association of psoriasis with coronary artery, cerebrovascular, and peripheral vascular diseases and mortality. Arch Dermatol. 2009 Jun;145(6):700-3.
4) El-Mongy S, Fathy H, Abdelaziz A, Omran E, George S, Neseem N, El-Nour N. Subclinical atherosclerosis in patients with chronic psoriasis: a potential association. J Eur Acad Dermatol Venereol. 2009 Nov 2
5) Balci DD, Balci A, Karazincir S, Ucar E, Iyigun U, Yalcin F, Seyfeli E, Inandi T, Egilmez E. Increased carotid artery intima-media thickness and impaired endothelial function in psoriasis. J Eur Acad Dermatol Venereol. 2009 Jan;23(1):1-6.
6) Tam LS, Shang Q, Li EK, Tomlinson B, Chu TT, Li M, Leung YY, Kwok LW, Wong KC, Li TK, Yu T, Zhu TY, Kun EW, Yip GW, Yu CM. Subclinical carotid atherosclerosis in patients with psoriatic arthritis. Arthritis Rheum. 2008 Sep 15;59(9):1322-31.
7) Eder L, Zisman D, Barzilai M, Laor A, Rahat M, Rozenbaum M, Bitterman H, Feld J, Rimar D, Rosner I. Subclinical atherosclerosis in psoriatic arthritis: a case-control study. J Rheumatol. 2008 May;35(5):877-82.
8) Gonzalez-Juanatey C, Llorca J, Amigo-Diaz E, Dierssen T, Martin J, Gonzalez-Gay MA. High prevalence of subclinical atherosclerosis in psoriatic arthritis patients without clinically evident cardiovascular disease or classic atherosclerosis risk factors. Arthritis Rheum. 2007 Aug 15;57(6):1074-80.
9) Meynadier J, Guilhou JJ, The biochemistry of psoriasis. Ann Dermatol Syphiligr (Paris). 1976;103(5-6):525-45.
10) A. Boyd, A. Menter, Erythrodermic psoriasis: Precipitating factors, course, and prognosis in 50 patients.Journal of the American Academy of Dermatology, 1989, Volume 21, Issue 5, Pages 985-991
11) Malina L, Volek V, Bielicky T. The activity of lactate dehydrogenase in the erythrocytes in psoriasis. Z Haut Geschlechtskr. 1969 Oct 1;44(19):877-9.
12) Shelling ML, Federman DG, Prodanovich S, Kirsner RS. Psoriasis and vascular disease: an unsolved mystery. Am J Med. 2008 May;121(5):360-5.
13) Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf

Acidity: The link between Atherosclerosis and Osteoporosis.

Although the prevalence of both atherosclerosis and osteoporosis increase with age, various and accumulating evidence indicate, since the initial studies (1, 2), a more direct relationship between these 2 conditions. Confirming this association, many recent studies have shown an increased carotid intima-media thickness (IMT), a marker for atherosclerosis, among women as they develop osteoporosis (3, 4).
A very recent study have reported that hip fracture is between two and five times more common in people with cardiovascular disease than in those with no history of the disease. The researchers from this study have found that bisphosphonates not only decrease the progression of osteoporosis, but also prevent the development of atherosclerosis and reduce total mortality rate (5).
Regarding this point it is interesting to note that bisphosphonates can reduce the elevated production of lactic acid in the body (6) what allow the acidity theory concept (7) to be a strong explanation for the link atherosclerosis/osteoporosis, taking in view the proposition from A. Wachman and D.S. Bernstein made in 1968 (8), and endorsed by others (9), that the body draws minerals from the bones to neutralize acid or alkaline challenges.
BTW, an editorial published at New England Journal of Medicine (Bone, Acid, and Osteoporosis, New England Journal of Medicine, V 330:1821-1822 , June 23, 1994) brings the following quote and comments:
"Life is a struggle, not against sin, not against the Money Power, not against malicious animal magnetism, but against hydrogen ions"1 Mencken H L. Exeunt omnes. Smart Set. 1919; 60: 138–145). These words, written by H.L. Mencken about the meaning of life and death, may also apply to the struggle of the healthy skeleton against the deleterious effects of retained acid.
Carlos Monteiro

1) Dent CE, Engelbrecht HE, Godfrey RC. Osteoporosis of lumbar vertebrae and calcification of abdominal aorta in women living in Durban. Br Med J. 1968;4:76-79.
2. Fujita T, Okamoto Y, Sakagami Y, Ota K, Ohata M. Bone changes and aortic calcification in aging inhabitants of mountain versus seacoast communities in the Kii Peninsula. J Am Geriatr Soc. 1984;32:124-128
3) J. Tamaki , M. Iki, Y. Hirano, Y. Sato, E. Kajita, S. Kagamimori, Y. Kagawa and H. Yoneshima. Low bone mass is associated with carotid atherosclerosis in postmenopausal women: The Japanese Population-based Osteoporosis (JPOS) Cohort Study , Osteoporosis International, V 20, N 1 / January, 2009
4) Hiroyuki Sumino, Shuichi Ichikawa, Shu Kasama, Takashi Takahashi, Hironosuke Sakamoto, Hisao Kumakura, Yoshiaki Takayama, Tsugiyasu Kanda, Masami Murakami and Masahiko Kurabayashi, Relationship between Carotid Atherosclerosis and Lumbar Spine Bone Mineral Density in Postmenopausal Women, Hypertension Research (2008) 31, 1191–1197;
5) Ulf Sennerby, Håkan Melhus, Rolf Gedeborg, Liisa Byberg, Hans Garmo, Anders Ahlbom, Nancy L. Pedersen, Karl Michaëlsson. Cardiovascular Diseases and Risk of Hip Fracture, JAMA. 2009;302(15):1666-1673.
6 Norman H. Bell and Ralph H. Johnson. Bisphosphonates in the treatment of osteoporosis, Endocrine, Volume 6, Number 2 / April, 1997.
7) Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
8) Wachman A, Bernstein DS. Diet and osteoporosis. Lancet. 1968;1:958–9.
9) Frances A. Tylavsky, Lisa A. Spence Laura Harkness. The Importance of Calcium, Potassium, and Acid-Base Homeostasis in Bone Health and Osteoporosis Prevention. J. Nutr. 138: 164S–165S, 2008 full free paper at http://jn.nutrition.org/cgi/reprint/138/1/164S

Lactate as cause of secondary damage in acute ischemic stroke

Atherosclerosis of the carotid arteries is a leading cause of ischemic stroke. Increased carotid artery intima-media thickness (IMT) is a marker of atherosclerosis and also a predictor for ischemic stroke that represents more than 80% of strokes, with the remainder due to hemorrhage.
Recent study involving 187 patients with acute ischemic stroke or transient ischemic attack (1) have indicated that lactate in cerebrospinal fluid, but not in blood, is a reliable marker for the metabolic crisis in acute ischemic stroke and a possible cause of secondary neuronal damage in cortical infarction resulting in unfavourable evolution in the sub acute phase of stroke and poor long-term outcome.
However, some researchers believe that whole blood lactate, as measured in this study, unlike serum lactate, is an unreliable measure of systemic lactate (2).
It is interesting to note that a study from 2004 found ischemic stroke acidosis-mediated activation of acid-sensing ion channels may play a role to ischemic damage of brain tissue (3).
Most interesting is that cardiac glycosides, besides its anti-atherosclerotic effects as discussed recently in this blog (4, 5), also can provide cerebral neuroprotection in front of ischemic stroke and in prevention of its occurrence (6).

1) Evaluation of lactate as a marker of metabolic stress and cause of secondary damage in acute ischemic stroke or TIA, Brouns R, Sheorajpanday R, Wauters A, Surgeloose DD, Mariën P, DE Deyn PP. Clinica Chimica Acta 397 (2008) 27–31
2) The Lactic Acid Response to Alkalosis in Panic Disorder: An Integrative Review Richard J. Maddock, M.D.J Neuropsychiatry Clin Neurosci 13:1, Winter 2001. Full free paper at http://neuro.psychiatryonline.org/cgi/content/full/13/1/22
3) Huang Y, McNamara JO. 2004. "Ischemic Stroke: “Acidotoxicity” Is a Perpetrator", Cell, Volume 118, Issue 6 , 17 September, Pages 665-666
4) The anti-atherosclerotic effects of cardiac glycosides, Carlos Monteiro at http://aciditytheory.blogspot.com/2009/11/anti-atherosclerotic-effects-of-cardiac_27.html
5) Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at http://www.infarctcombat.org/AcidityTheory.pdf
6) Cardiac Glycosides in Prevention of Stroke, Carlos Monteiro, ICP, July 10, 2006, Full text at http://www.infarctcombat.org/media/071006.html