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Blood Pressure And Body Fat

sphygmomanometerIf you’re in the upper part of your normal weight range or are outright overweight, you might want to do something about it, especially if you’re getting up there in age.  The relationship between being overweight and having high blood pressure is well-established.

The upper part of the normal blood pressure range can be a danger zone for heart attack and stroke.  Investigators at Kaiser Permanente, in Portland, Oregon, looked at almost 600 men and women who were ten to sixty-five percent above their ideal weight, and who had slightly elevated blood pressure.  All were given weight reduction counseling, and later were compared to a like-sized group who received no such guidance.  It was found that a ten-pound weight loss effected a drop in diastolic (bottom number) blood pressure by 2.7 mm of mercury, which doesn’t sound like a lot, but which is significant.  For those who dropped twenty pounds, diastolic pressure dropped by 7 mm of Hg.  During this 3-year study, those who managed to keep the weight off also managed to keep their blood pressure under control, as opposed to the control group.  “Clinically significant long-term reductions in blood pressure and reduced risk for hypertension can be achieved with even modest weight loss” is the conclusion.  (Stevens. 2001)

Though a decade old, the cited study is pertinent.  The dietary habits of Americans are paving a road to dereliction by creating serious health concerns that include obesity, diabetes, CVD, and hypertension.  For every pound of fat above your ideal weight, you might be adding miles of blood vessels.  Although fat doesn’t need the vasculature that muscle does, it needs to be fed nonetheless.  If you were to add another hundred feet to your garden hose, you’d notice the water dripping out the end instead of flowing with purpose.  Unless you have a pump, you’ll not likely increase water pressure.  Your heart, on the other hand, will notice a need for increased pressure to get blood to the other end of the line and will do just that—increase the pressure.  If this goes on for too long, it just might start giving you trouble.

The Dietary Approach to Stop Hypertension (DASH) has been deemed an effective management tool.  Lifestyle modifications and salt reduction, along with a diet filled with fruits and vegetables, nuts and seeds, eliminating / limiting saturated and trans-fats and empty calories, was found to be effective in reducing blood pressure by considerable margins.  Those with the highest blood pressure realized the greatest benefits.  (Kolaska.  1999)  Exercise alone can lower blood pressure, but it’s not going to happen until you do it.  Combined with a behavioral weight loss program, even a modicum of exercise will show an enhanced effect.  (Blumenthal.  2000)  Health of the entire cardiovascular system is at stake, and the rewarded decrease in ventricular mass and wall thickness should be motivation enough to get an overweight hypertensive guy movin’ and shakin’.  The improvements in peripheral vascular health are also measurable, and conditions such as peripheral arterial disease may be forestalled.  (Bacon.  2004)

The development of obesity causes significant changes inside the body, things you can’t see.  Extra blood vessel formation is one such change.  And the accumulation of fat around the middle and the accompanying elevation in blood pressure may change lifestyle in an unwanted direction.

References

Stevens VJ, Obarzanek E, Cook NR, Lee IM, Appel LJ, Smith West D, Milas NC, Mattfeldt-Beman M, Belden L, Bragg C, Millstone M, Raczynski J, Brewer A, Singh B, Cohen J;
Trials for the Hypertension Prevention Research Group.
Long-term weight loss and changes in blood pressure: results of the Trials of Hypertension Prevention, phase II.
Ann Intern Med. 2001 Jan 2;134(1):1-11.

Kolasa KM.
Dietary Approaches to Stop Hypertension (DASH) in clinical practice: a primary care experience.
Clin Cardiol. 1999 Jul;22(7 Suppl):III16-22.

Blumenthal JA, Sherwood A, Gullette EC, Babyak M, Waugh R, Georgiades A, et al
Exercise and weight loss reduce blood pressure in men and women with mild hypertension: effects on cardiovascular, metabolic, and hemodynamic functioning.
Arch Intern Med. 2000 Jul 10;160(13):1947-58.

Bacon SL, Sherwood A, Hinderliter A, Blumenthal JA
Effects of exercise, diet and weight loss on high blood pressure.
Sports Med. 2004;34(5):307-16.

Lijnen HR.
Angiogenesis and obesity
Cardiovasc Res (2008 May 1); 78 (2): 286-293.

Blumenthal JA, Babyak MA, Hinderliter A, Watkins LL, Craighead L, et al
Effects of the DASH diet alone and in combination with exercise and weight loss on blood pressure and cardiovascular biomarkers in men and women with high blood pressure: the ENCORE study
Arch Intern Med. 2010 Jan 25;170(2):126-35.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Cholesterol Limbo: Can You Go Too Low?

good-and-bad-cholesterolFor many years cholesterol has been denigrated as a factor in heart disease, when all along it was only a spectator at the scene of the accident. Although it’s been the topic of many conversations throughout its public life, cholesterol is misunderstood by many people… who don’t really know what it is. Because it isn’t soluble in water, but only in organic solvents, cholesterol is classified as a lipid. It’s the major steroid in the body, with the greatest concentrations in the myelin sheath that surrounds nerves and in the plasma membrane that encircles each of the trillions of cells from which we are made.  In the membrane, it prevents deformation and decreases permeability to small water-soluble molecules. Without cholesterol, such as in a bacterium or plant, our cells would need cell walls. Beyond its stability-inducing structural role, where it sits parallel to the phospholipids that afford both structure and function to the membrane, cholesterol exerts its character in the manufacture of several hormones, including cortisol, cortisone, and aldosterone in the adrenal glands, and in the formation of the sex hormones progesterone, estrogen, and testosterone. Without it, the body can make neither vitamin D from exposure to the sun, nor the bile made by the liver for the digestion of fats.

Though cholesterol may eventuate cardiovascular entailments for those so susceptible, as would be such for people with existing coronary disease, heavy smokers, those with a family history of CVD (Cardio Vascular Disease), or those who have already suffered a cardiac episode, it is a generally benign molecule that supports membrane function and fluidity. That cholesterol which exists outside the membrane as an extracellular entity may contribute to the cascade of events that leads to the cell proliferation characteristic of the early stages of atherosclerosis.

But low cholesterol may also be a concern, where a disturbed balance between the uptake of cholesterol from lipoproteins and cholesterol efflux may cause the formation of foam cells, which can accumulate in the linings of arteries and cause additional accretion of platelets and other components of blood that can form an atheroma, or plaque. In Chapman’s work it was noted that massive foam cell formation by tissue macrophages may occur despite the absence of lipid accumulation in the vascular wall (Chapman, 2008). Outside the realm of cardiac episodes reside pathologies attributable to hypocholesterolemia (low cholesterol). Such is the case with endotoxic infections that occasionally accompany critical illness and contribute to capillary permeability and fever. This latter condition may arise following the death of a (usually gram-negative) bacterium that gets broken down in the body. In the attempt to rectify the matter, healthcare workers are advised to correct hypolipidemia by administering a reconstituted high-density lipoprotein preparation as both prevention and treatment (Gordon, 1996). Additionally, a correlation has been made between low cholesterol and the presence of immune markers called interleukins, which are regulatory proteins released by cells in the immune system (Gordon, 2001). Herein lies the inference that cholesterol has immunomodulatory properties (Miguez, 2010) (Bukrinsky, 2006).

From other perspectives, cholesterol levels below 160 mg/dL are associated with all-cause mortality other than cardiovascular disease, especially with cancer, respiratory and digestive diseases, violent deaths that include suicide, and hemorrhagic stroke, leading researchers to question the validity of prescribing anti-cholesterol drugs for those persons without additional CVD risks (Meilahn, 1995) (Nago, 2011). In the Honolulu Heart Study, it was noted in six thousand subjects that falling levels of cholesterol were linked to an excess risk of liver disease and cancer, but that stable levels were not (Iribarren, 1995). Previous work identified low cholesterol as causative of early death, where it was concluded that women in particular experience no relationship between high cholesterol levels and cardiovascular events, but that the opposite may apply to most men, leading to a decision not to treat females unless there exists active coronary disease (Hulley, 1992). Hemorrhagic stroke risk may increase by twofold in males with cholesterol levels below 160, but higher values may be protective against cancers of the lung and the lymphatic and hematopoietic systems, and COPD (Chronic Obstructive Pulmonary Disease) (Neaton, 1992). From these and other studies, we may infer that any prolonged treatment with statin or other drugs be closely watched, especially in light of the indication that low cholesterol levels are also associated with suicide and depression (Atmaca, 2008) (Lester, 2002) (Partonen, 1999). Basically, then, control of cholesterol levels needs consistency for cell signaling mechanisms to function at peak efficiency, else the machinery deals with faulty information and results in sickness.

The Canadians have decided that cholesterol intake is not a concern, since dietary cholesterol, as found in eggs, for example, does not become part of serum cholesterol, and even if it did, influence is insignificant. Simultaneously, saturated and trans fats instead are deemed to be primary determinants of serum total cholesterol and troublesome LDL (McDonald, 2004). Life exists at the cellular level. Without cholesterol, membranes would be too fluid. Like the masts that hold a circus tent erect, cholesterol maintains the architecture of the cell and keeps phospholipids far enough apart to prevent them from clumping and becoming disorganized. In this way, everything walks to the beat of the same drummer.

References

Abbott C, Meadows AB, Lier K.
Low cholesterol and noncardiovascular mortality.
Mil Med. 2000 Jun;165(6):466-9.


Atmaca M, Kuloglu M, Tezcan E, Ustundag B.
Serum leptin and cholesterol values in violent and non-violent suicide attempters.
Psychiatry Res. 2008 Feb 28;158(1):87-91. Epub 2007 Dec 26.


Michael Bukrinsky and Dmitri Sviridov
Human immunodeficiency virus infection and macrophage cholesterol metabolism
Journal of Leukocyte Biology. Nov 2006; 80(5):  1044-1051


Chapman MJ, Huby T, Van Berkel TJ, Van Eck M.
Coexistence of foam cells and hypocholesterolemia in mice lacking the ABC transporters A1 and G1.
Out R, Jessup W, Le Goff W, Hoekstra M, Gelissen IC, Zhao Y, Kritharides L, Chimini G, Kuiper J,
Circ Res. 2008 Jan 4;102(1):113-20. Epub 2007 Oct 25.


Epstein FH.
Relationship between low cholesterol and disease. Evidence from epidemiological studies and preventive trials.
Ann N Y Acad Sci. 1995 Jan 17;748:482-90.


Fagot-Campagna A, Hanson RL, Narayan KM, Sievers ML, Pettitt DJ, Nelson RG, Knowler WC.
Serum cholesterol and mortality rates in a Native American population with low cholesterol concentrations: a U-shaped association.
Circulation. 1997 Sep 2;96(5):1408-15.


Fang Xu, Scott D. Rychnovsky, Jitendra D. Belani, Helen H. Hobbs, Jonathan C. Cohen, and Robert B. Rawson
Dual roles for cholesterol in mammalian cells
Proc Natl Acad Sci U S A. 2005 October 11; 102(41): 14551–14556.


Gordon BR, Parker TS, Levine DM, Saal SD, Wang JC, Sloan BJ, Barie PS, Rubin AL.
Low lipid concentrations in critical illness: implications for preventing and treating endotoxemia.
Crit Care Med. 1996 Apr;24(4):584-9.


Gordon BR, Parker TS, Levine DM, Saal SD, Wang JC, Sloan BJ, Barie PS, Rubin AL.
Relationship of hypolipidemia to cytokine concentrations and outcomes in critically ill surgical patients.
Crit Care Med. 2001 Aug;29(8):1563-8.


Henna Ohvo-Rekila , Bodil Ramstedt, Petra Leppimaki, J. Peter Slotte
Cholesterol interactions with phospholipids in membranes
Progress in Lipid Research 41 (2002) 66–97


Hulley SB, Walsh JM and Newman TB
Health policy on blood cholesterol. Time to change directions.
Circulation. 1992; 86: 1026-1029


Iribarren C, Reed DM, Chen R, Yano K, Dwyer JH.
Low serum cholesterol and mortality. Which is the cause and which is the effect?
Circulation. 1995 Nov 1;92(9):2396-403.


Jacobs D, Blackburn H, Higgins M, Reed D, Iso H, McMillan G, Neaton J, Nelson J, Potter J, Rifkind B, et al.
Report of the Conference on Low Blood Cholesterol: Mortality Associations.
Circulation. 1992 Sep;86(3):1046-60.


Lester D.
Serum cholesterol levels and suicide: a meta-analysis.
Suicide Life Threat Behav. 2002 Fall;32(3):333-46.


Lijnen P, Echevaría-Vázquez D, Petrov V.
Influence of cholesterol-lowering on plasma membrane lipids and function.
Methods Find Exp Clin Pharmacol. 1996 Mar;18(2):123-36.


McDonald BE.
The Canadian experience: why Canada decided against an upper limit for cholesterol.
J Am Coll Nutr. 2004 Dec;23(6 Suppl):616S-620S.


Elaine N. Meilahn, MD
Low Serum Cholesterol–-Hazardous to Health?
Circulation. 1995; 92: 2365-2366


Míguez MJ, Lewis JE, Bryant VE, Rosenberg R, Burbano X, Fishman J, Asthana D, Duan R, Madhavan N, Malow RM.
Low cholesterol? Don’t brag yet … hypocholesterolemia blunts HAART effectiveness: a longitudinal study.
J Int AIDS Soc. 2010 Jul 13;13:25.


Nago N, Ishikawa S, Goto T, Kayaba K.
Low cholesterol is associated with mortality from stroke, heart disease, and cancer: the Jichi Medical School Cohort Study.
J Epidemiol. 2011;21(1):67-74. Epub 2010 Dec 11.


Neaton JD, Blackburn H, Jacobs D, Kuller L, Lee DJ, Sherwin R, Shih J, Stamler J, Wentworth D.
Serum cholesterol level and mortality findings for men screened in the Multiple Risk Factor Intervention Trial. Multiple Risk Factor Intervention Trial Research Group.
Arch Intern Med. 1992 Jul;152(7):1490-500.


News-Medical. Net
Novel role for cholesterol inside the cell
Published on March 7, 2005 at 3:18 AM
http://www.news-medical.net/news/2005/03/07/8198.aspx


Partonen T, Haukka J, Virtamo J, Taylor PR, Lönnqvist J.
Association of low serum total cholesterol with major depression and suicide.
Br J Psychiatry. 1999 Sep;175:259-62.


Suarez EC.
Relations of trait depression and anxiety to low lipid and lipoprotein concentrations in healthy young adult women.
Psychosom Med. 1999 May-Jun;61(3):273-9.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Salt’s At Fault? Now What?

too_much_saltFor years it was held that salt intake has a distinct influence on blood pressure and cardiovascular disease (CVD). In fact, in 2011 the American Heart Association issued a sweeping call for salt restriction (Appel, 2011), limiting intake of sodium to less than 1500 milligrams a day, which translates to approximately 3750 milligrams of sodium chloride. One teaspoon of salt, which is about 40% sodium and 60% chloride, has 2300 mg of sodium. Naturally found in most foods, sodium defies accurate measurement, but because men eat more food than women, they consume more. Nerve impulses depend on sodium for activation; otherwise you wouldn’t be able to open the link to this page. Overconsumption of sodium, however, can lead to calcium deficiency (Teucher, 2008). Once again, it’s a matter of balance…but not without at least a little controversy. Also in 2011, the Journal of the American Medical Association published a paper that discounts a relationship of salt intake to CVD. In a study that lasted for nearly eight years, researchers found the incidence of mortality and morbidity related to sodium intake to be minimal, with no translation to a greater risk of elevated blood pressure or CVD (Stolarz-Skrzypek, 2011). Contrary to conventional wisdom, low sodium was associated with elevated CVD risk. Now there, don’t jump for joy and a box of pretzels over one study. For every yin there’s a yang—potassium is the foil to sodium. Potassium is a mineral whose insufficiency is widespread. Most of us are fortunate if we get half the 4700 mg recommended every day. Maintaining the ratio, 2 to 1 in favor of potassium, offers considerable benefit to cardiovascular health (Yang, 2011). The bottom line in all this is that minerals need to be in, well, balance.

Still, excess salt intake is a way of life for some. In a fancy restaurant, you might be challenged to find salt and pepper shakers on a table, for fear of insulting the chef. At the corner diner, on the other hand… This temptation, or rather succumbing to the temptation, could be our downfall. Very recent papers published in the highly respected journal, Nature, deliver the news that salt intake may be associated with autoimmune diseases through a mechanism that turns certain of our immune cells into traitors. In autoimmune conditions, abnormal antibodies are produced and they attack the body’s own cells and tissues. Lupus, rheumatoid arthritis and type 1 diabetes are commonly known examples, but there are other disorders that have an autoimmune component. In each instance there will be a characteristic set of autoantibodies to attack normal cells. Sometimes the autoantibodies actually cause the tissue and organ damage; sometimes they’re only the markers of disease. Susceptibility to autoimmune disease could be blamed on environmental influences, genetic makeup, exposure to an infectious organism, or to a combination of these.

Newly identified in the study of autoimmune disease is a population of T cells called TH17, which produce an interleukin different from the run-of-the-mill T cells that assist other white cells in immunologic processes. Excessive numbers of TH17 cells are thought to play a vital role in autoimmune diseases (Harrington, 2005) (Stockinger, 2007), including multiple sclerosis, psoriasis, rheumatoid arthritis and Crohn’s disease. What these cells do is to fail to turn inflammation off. Inflammation is the body’s response to attack, whether from trauma, viral or bacterial infection, heat or whatever else might cause an insult. In this response a few things happen: blood vessels dilate, fluid may leak from the surrounding area and clot, cells swell, platelets get activated, macrophages show up to swallow damaged tissue, and the healing begins. We need inflammation to heal, but it has to stop before healing is complete. We take anti-inflammatory chemicals to stop the pain, but we also stop—or at least inhibit—the healing. TH17 cells are there to fight infections, normally targeting fungi and bacteria, but they need to control themselves. One of the factors found to instigate TH17 cells into aberrant activity is salt. In its presence, T helper cells are more likely to develop into TH17 cells that are pathogenic (Wu, 2013). Then they attack the body’s own cells.

Not surprising is that those who frequent fast-food joints were found to have elevated levels of TH17 cells. Why not, if this relationship is definitive?  Such establishments use salt to embellish flavor. Each of us has a gene that controls the physiological response to salt intake. In certain individuals, this gene is over-expressed by salt, leading to the pathogenicity of TH17 cells and subsequent inflammation (Wu, 2013). This effect is leading scientists to look more closely at low-salt diets in the treatment of autoimmune diseases. The good side of the original study is that several genes are implicated in the response, not just the one with the greatest impact. And it’s not likely that all are out of sync at the same time. Furthermore, the factors that initiate autoimmune disease need to be in concert. For most of us, they are not. For the rest, maybe hiding the salt shaker could make a difference. For those with type 2 diabetes, the difference would be substantial.

References

Appel LJ, Frohlich ED, Hall JE, Pearson TA, Sacco RL, Seals DR, Sacks FM, Smith SC Jr, Vafiadis DK, Van Horn LV.
The importance of population-wide sodium reduction as a means to prevent cardiovascular disease and stroke: a call to action from the American Heart Association.
Circulation. 2011 Mar 15;123(10):1138-43. doi: 10.1161/CIR.0b013e31820d0793. Epub 2011 Jan 13.

Charlton K, Yeatman H, Houweling F, Guenon S.
Urinary sodium excretion, dietary sources of sodium intake and knowledge and practices around salt use in a group of healthy Australian women.
Aust N Z J Public Health. 2010 Aug;34(4):356-63. doi: 10.1111/j.1753-6405.2010.00566.x.

Cook NR, Obarzanek E, Cutler JA, Buring JE, Rexrode KM, Kumanyika SK, Appel LJ, Whelton PK; Trials of Hypertension Prevention Collaborative Research Group.
Joint effects of sodium and potassium intake on subsequent cardiovascular disease: the Trials of Hypertension Prevention follow-up study.
Arch Intern Med. 2009 Jan 12;169(1):32-40. doi: 10.1001/archinternmed.2008.523.

Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT.
Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages.
Nat Immunol. 2005 Nov;6(11):1123-32. Epub 2005 Oct 2.

Su M. Metcalfe
Multiple sclerosis: One protein, two healing properties
Nature. (15 September 2011); 477: 287–288 doi:10.1038/477287a

John J. O’Shea & Russell G. Jones
Autoimmunity: Rubbing salt in the wound
Nature. 06 March 2013 doi:10.1038/nature11959

Steinman L.
A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage.
Nat Med. 2007 Feb;13(2):139-45.

Stockinger B, Veldhoen M.
Differentiation and function of Th17 T cells.
Curr Opin Immunol. 2007 Jun;19(3):281-6. Epub 2007 Apr 12.

Stolarz-Skrzypek K, Kuznetsova T, Thijs L, Tikhonoff V, Seidlerová J, Richart T, Jin Y et al
Fatal and nonfatal outcomes, incidence of hypertension, and blood pressure changes in relation to urinary sodium excretion.
JAMA. 2011 May 4;305(17):1777-85. doi: 10.1001/jama.2011.574.

Teucher B, Dainty JR, Spinks CA, Majsak-Newman G, Berry DJ, Hoogewerff JA, Foxall RJ, Jakobsen J, Cashman KD, Flynn A, Fairweather-Tait SJ.
Sodium and bone health: impact of moderately high and low salt intakes on calcium metabolism in postmenopausal women.
J Bone Miner Res. 2008 Sep;23(9):1477-85. doi: 10.1359/jbmr.080408.

Chuan Wu, Nir Yosef, Theresa Thalhamer, Chen Zhu, Sheng Xiao, Yasuhiro Kishi, Aviv Regev & Vijay K. Kuchroo
Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1
Nature. 06 March 2013 doi:10.1038/nature11984

Yang Q, Liu T, Kuklina EV, Flanders WD, Hong Y, Gillespie C, Chang MH, Gwinn M, Dowling N, Khoury MJ, Hu FB.
Sodium and potassium intake and mortality among US adults: prospective data from the Third National Health and Nutrition Examination Survey.
Arch Intern Med. 2011 Jul 11;171(13):1183-91. doi: 10.1001/archinternmed.2011.257.

Nir Yosef, Alex K. Shalek, Jellert T. Gaublomme, Hulin Jin, Youjin Lee, Amit Awasthi, et al
Dynamic regulatory network controlling TH17 cell differentiation
Nature. 06 March 2013 doi:10.1038/nature11981

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Statins And Diabetes: Why Didn’t They Tell Me?

heart-measureCan you tell when you’ve eaten too much ice cream? Does the eructation shake your table lamps after too many sodas? Sometimes we learn what enough is by having too much. Too bad it isn’t the same with drugs. A hundred-pound lady doesn’t need as many aspirins to get rid of a headache as a two-hundred-pound guy. And for those who take a statin because the doctor said so, why does everybody start with the same doses? With Zocor, everybody starts with 40 mg. Doesn’t anybody think that maybe 5 mg could do the trick? Hey, if one quart of white semi-gloss will cover the bathroom walls adequately, why buy a gallon unless you have a use for it elsewhere? You gonna paint those walls until the gallon is empty?

Over the last few years, the cholesterol model of cardiovascular disease is steadily being replaced by the inflammation model of CVD, putting statin drugs on the back burner because cholesterol, it is realized, has never caused a heart attack. In fact, half the scary cardiac events happen to people who have what are deemed ideal cholesterol numbers (Sachdeva, 2009). Yes, it is true that statins interfere with cholesterol manufacture by the body, not only in the liver, but also in the brain, where cholesterol is vital to the machinery of thought and function. Low cholesterol can lead to serious health issues when that machinery is interrupted.  Low cholesterol levels are associated with high total mortality, even in patients with coronary heart disease (Behar, 1997) (Krumholz, 1994).

Differences between young and old, and between male and female, are recognized in the cholesterol arena, too. The impact of total cholesterol as a risk factor for heart disease decreases with age (Waverling-Rijnsburger, 1997) and for women, whose moderately elevated cholesterol may actually be beneficial (Petursson, 2012). The age cutoff for both genders is fifty (Anderson, 1987). If this information regarding age was known ten years ago, why are TV ads so adamant about getting cholesterol values below a hundred?

The personal experiences of at least one NASA astronaut have attested to the nasty effects of statins, including transient global amnesia, impaired cognition, personality changes, myopathy, neuropathy and neuromuscular degeneration. The root of all these maladies is the inhibition of Co-enzyme Q 10, a physiologically necessary substance that is blocked by Lipitor, Zocor, Crestor and the rest of the gang. Without CoQ10, mitochondria don’t work their magic at cell metabolism, where they get to burn food for energy, oxidize fatty acids, and use the electrons supplied by CoQ10 for a host of other essential activities. The pathway that makes cholesterol also makes CoQ10 in the body. Stopping one stops the other. This is so well known that statin prescriptions in Canada—for Mevachor®, Pravachol® and Lipitor®— contain a warning about CoQ 10 depletion. Merck even filed two patents for a statin-CoQ 10 combination, no. 4,933,165 and no. 4,929,437, which expired in May and June of 2007 (Koon, 2013). And you thought the drug companies had your best interest at heart, eh? The cholesterol issue is a complicated one and now, to add to the quagmire of hits and misses, is the notice that statins are implicated in the risk of developing diabetes. The endearing stars in this drama are atorvastatin (Lipitor), rosuvastatin (Crestor) and simvastatin (Zocor), brought to you by Pfizer, AstraZeneca and Merck. Atorvastatin was found to be the most influential of the three at elevating blood glucose, followed by rosuvastatin and simvastatin, in a recent Canadian study carried out at the Toronto General Hospital (Carter, 2013). From this work it may be drawn that pravastatin (Pravachol) is the safest drug related to diabetes onset. Regardless of drug of choice, or rather the physician’s choice, dose intensity also seems to make a difference in diabetes risk. Intense doses, especially at 80 mg of Zocor, increase the odds of all statin-induced adverse events (Silva, 2007), extending diabetes risk to almost ten percent of the medicated population (Preiss, 2011).

For all the hoopla that accompanied statins’ debut forty years ago into the pharmaceutical world, recounting their anti-cholesterol beneficence, it’s been discovered that their real claim to fame is being anti-inflammatory. That characteristic, it’s claimed, is more important to their raison d’etre than disrupting the cholesterol (and CoQ 10) pathway (Antonopoulos, 2012) (Mora, 2006) (Weitz-Schmidt, 2002). If so, then anti-inflammatory substances that have zero side effects might be considered. In this list will be simple things with complex mechanisms, like ginger, curcumin (from turmeric), capsaicin (from hot peppers), garlic, fish oil, bromelain (from pineapples), flaxseed oil, and zinc, among others. Aside from an allergic reaction which you already would know about, the only side effects of these ingredients are possibly foul breath (that would be the anti-vampire action) and stomach upset from too much of a good thing.

The mention of CoQ10 needs at least a little thought. Natural stores of this enzyme diminish with age. The fact that it donates electrons to multiple body processes bespeaks its importance to full function. It’s comparable to using the correct gauge extension cord with an electric weed trimmer. If the cord can’t carry the voltage, the trimmer will not work to its potential. Adding CoQ 10 to the daily regimen is a prudent decision whether taking a statin or not. Why?  It helps to control blood glucose (Kolahdouz, 2013) (Mezawa, 2012).

References

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Carter AA, Gomes T, Camacho X, Juurlink DN, Shah BR, Mamdani MM.
Risk of incident diabetes among patients treated with statins: population based study.
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Richard Deichmann, MD, Carl Lavie, MD, and Samuel Andrews, MD
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Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study
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Risto Huupponen, Jorma Viikari
Statins and the risk of developing diabetes
BMJ. 23 MAY 2013;346:f3156

Kolahdouz Mohammadi R, Hosseinzadeh-Attar MJ, Eshraghian MR, Nakhjavani M, Khorami E, Esteghamati A.
The effect of coenzyme Q10 supplementation on metabolic status of type 2 diabetic patients.
Minerva Gastroenterol Dietol. 2013 Jun;59(2):231-6.

Koon, Robin
CoQ 10 Supplementation with Statins
Natural Products Insider. Feb 26, 2013

Kozarevic D, McGee D, Vojvodic N, Gordon T, Racic Z, Zukel W, Dawber T.
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Mezawa M, Takemoto M, Onishi S, Ishibashi R, Ishikawa T, Yamaga M, Fujimoto M, Okabe E, He P, Kobayashi K, Yokote K.
The reduced form of coenzyme Q10 improves glycemic control in patients with type 2 diabetes: an open label pilot study.
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Mora S, Ridker PM.
Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER)–can C-reactive protein be used to target statin therapy in primary prevention?
Am J Cardiol. 2006 Jan 16;97(2A):33A-41A.

Steven E. Nissen, M.D., E. Murat Tuzcu, M.D., Paul Schoenhagen, M.D., Tim Crowe, B.S., et al
Statin Therapy, LDL Cholesterol, C-Reactive Protein, and Coronary Artery Disease
N Engl J Med. January 6, 2005; 352:29-38

Preiss D, Seshasai SR, Welsh P, Murphy SA, Ho JE, Waters DD, DeMicco DA, Barter P, et al
Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis.
JAMA. 2011 Jun 22;305(24):2556-64.

Paul M Ridker, M.D., Christopher P. Cannon, M.D., David Morrow, M.D., Nader Rifai, Ph.D, et al
C-Reactive Protein Levels and Outcomes after Statin Therapy
N Engl J Med. Jan 6, 2005; 352:20-28

Rudman D, Mattson DE, Nagraj HS, Caindec N, Rudman IW, Jackson DL.
Antecedents of death in the men of a Veterans Administration nursing home.
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Sachdeva A, Cannon CP, Deedwania PC, Labresh KA, Smith SC Jr, Dai D, Hernandez A, Fonarow GC.
Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136,905 hospitalizations in Get With The Guidelines.
Am Heart J. 2009 Jan;157(1):111-117.e2.

Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, Seshasai SR et al
Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials.
Lancet. 2010 Feb 27;375(9716):735-42.

Sattar N, Taskinen MR.
Statins are diabetogenic–myth or reality?
Atheroscler Suppl. 2012 Aug;13(1):1-10.

Shah RV, Goldfine AB.
Statins and risk of new-onset diabetes mellitus.
Circulation. 2012 Oct 30;126(18):e282-4. doi: 10.1161/CIRCULATIONAHA.112.122135.

Silva M, Matthews ML, Jarvis C, Nolan NM, Belliveau P, Malloy M, Gandhi P.
Meta-analysis of drug-induced adverse events associated with intensive-dose statin therapy.
Clin Ther. 2007 Feb;29(2):253-60.

Simsek S, Schalkwijk CG, Wolffenbuttel BH.
Effects of rosuvastatin and atorvastatin on glycaemic control in Type 2 diabetes—the CORALL study.
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Sukhija R, Prayaga S, Marashdeh M, Bursac Z, Kakar P, Bansal D, Sachdeva R, Kesan SH, Mehta JL.
Effect of statins on fasting plasma glucose in diabetic and nondiabetic patients.
J Investig Med. 2009 Mar;57(3):495-9.

Gabriele Weitz-Schmidt
Statins as anti-inflammatory agents
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Total cholesterol and risk of mortality in the oldest old.
Lancet. 1997 Oct 18;350(9085):1119-23.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

The Sweet Sweep of Sleep

sleepy-womanAhh, the sweet balm that soothes the nerves and restores the soul at the end of the day. Sadly, for some of us it is elusive, and its intangible rewards sporadic. Sleep. It can get interrupted, disrupted and corrupted. Even in its worst state, sleep can be the most desired gift for the time.

There have been thousands of sleep studies over the years, but science still isn’t completely sure why we need it. “Completely” is the key word. One goofy answer is that we sleep to cure sleepiness. It’s agreed that sleep gives the body a chance to rejuvenate. That we know about rapid eye movement sleep (REM) shows that sleep is not a totally static process for the brain. Asleep, it still needs calories. The amount of sleep a person needs is purely singular, and depends on his or her circadian rhythm, which is that twenty-four-hour cycle of biological activities that occur regularly and dependably regardless of illumination. What sleep experts look for are maximum melatonin levels and minimum core body temperature, reporting that one should be asleep at least six hours before lowest temp is achieved. When these occur just after the middle of the sleep cycle, the timing is deemed to be just right (Wyatt, 1999) (Dijk, 2002) (Taillard, 2011).

Too much sleep can be as unhealthy as too little. Where lack of sleep can increase the chance of accidents and CVD issues, a plethora might increase risk of other-cause mortality (Ferrie, 2007). Because animals with brains sleep, we might infer that it’s a needed pastime. Regardless of who and how much, the fact is that we heal better when we sleep, the immune system gets a chance to recoup, memory and cognitive function improve, and a general restoration takes place. And now there’s another reason to cut Z’s…the prevention of Alzheimer’s disease and related cognitive disorders.

Whether it’s more hypothetical than proven, a new study released by the University of Rochester hints that a good night’s sleep can ward off Alzheimer’s disease (Xie, 2013). Lead author, Maiken Nedergaard, notes that sleep serves a vital function, a collective term that includes washing debris out of the brain. The brain produces toxic waste as it works every day. This new study says that while we sleep the brain shrinks in size, allowing the spaces between brain cells to enlarge so that junk can be washed out by the cerebral spinal fluid that is pumped around it (Underwood, 2013).

Researchers in Nedergaard’s lab noticed that mice whose brains were probed while conscious would sometimes fall asleep. When that happened, cerebrospinal fluid would rush into the brain’s interstitial space and wash away cellular debris. Delving into the phenomenon, they observed that the brain’s glial cells, a web of connective tissue that supports neurons, expand during wakefulness to reduce the space between cells and shut off the movement of fluid. During sleep, the interstitial volume changes again.

Interstitial fluid is a solution that bathes the area around cells with a concoction that contains sugars, salts, fatty acids, amino acids, coenzymes, hormones, and neurotransmitters. Different areas of the body have different concentrations of these substances. Little attention was paid to the area between cells before Nedergaard’s investigation because that was considered just space (Herculano-Houzel, 2013).  The brain’s drainage system was termed the glymphatic system, a functional waste management setup that removes extracellular proteins and metabolic waste products from the pathway, but reliant upon the glia instead of a dedicated, albeit absent, lymphatic network.

To double-check their findings, scientists injected the mouse brains with proteins that parallel those implicated in Alzheimer’s disease (AD)—the amyloids. These were washed away faster from the brains of sleeping mice than their awake peers. It is the accumulation of these soluble proteins at the synapses that is believed by some to initiate the disease (Tomiyama, 2010) (Esparza, 2013).

Fragmented sleep is that which does not include much slow-wave sleep and is not refreshing. Total time asleep is less than normal, affecting about a third of all adults. Unfragmented-consolidated sleep is divided into two periods with a gap between. This “bi-phasic” sleep is common and is something people can adjust to. Fragmented sleep is characteristic of Alzheimer’s and Parkinson’s patients, though it is common to the aging process. However, there is debate about whether increased fragmentation is a normal part of aging or indicative of an underlying pathology. Regardless, it is associated with cognitive performance (Lim, 2013). In any case, it’s unpleasant to experience the next day’s sleepiness. There are pharmaceutical sleep aids, but the natural ones, such as valerian and melatonin, are safer.

Melatonin is produced in the brain, but decreases with age and in those with Alzheimer’s disease. There are data from clinical trials demonstrating that melatonin can slow the progression of cognitive impairment in AD patients by protecting neural cells from amyloid-mediated toxicity and by arresting the formation of plaques in the first place (Lin, 2013). As a noted anti-oxidant, melatonin is able to scavenge the free radicals that are likewise implicated in AD etiology (He, 2010), and to improve mitochondrial energy metabolism (Cheng, 2006) (Liu, 2013). Produced in the pineal gland from tryptophan, melatonin, as a sleep aid, lowers body temperature and blood pressure, a condition required for sound sleep.

If sleep can clear the abnormal accumulation of neurotoxins (Rothman, 2012), and if melatonin can help resolve dysfunctional sleep patterns, then this bag of ideas might just hold more than water.

References

Orfeu M. Buxton, Sean W. Cain, Shawn P. O’Connor, James H. Porter, Jeanne F. Duffy,
Wei Wang, Charles A. Czeisler and Steven A. Shea
Adverse Metabolic Consequences in Humans of Prolonged Sleep Restriction Combined with Circadian Disruption
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Cheng Y, Feng Z, Zhang QZ, Zhang JT.
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Daniel A. Cohen, Wei Wang, James K. Wyatt, Richard E. Kronauer, Derk-Jan Dijk, Charles A. Czeisler and Elizabeth B. Klerman
Uncovering Residual Effects of Chronic Sleep Loss on Human Performance
Sci Transl Med. 13 January 2010; Vol. 2 Issue 14: p. 14ra3

Dijk DJ, Lockley SW.
Integration of human sleep-wake regulation and circadian rhythmicity.
J Appl Physiol. 2002 Feb;92(2):852-62.

Dragicevic N, Copes N, O’Neal-Moffitt G, Jin J, Buzzeo R, Mamcarz M, Tan J, Cao C, Olcese JM, Arendash GW, Bradshaw PC.
Melatonin treatment restores mitochondrial function in Alzheimer’s mice: a mitochondrial protective role of melatonin membrane receptor signaling.
J Pineal Res. 2011 Aug;51(1):75-86.

Dragicevic N, Smith A, Lin X, Yuan F, Copes N, Delic V, Tan J, Cao C, Shytle RD, Bradshaw PC.
Green tea epigallocatechin-3-gallate (EGCG) and other flavonoids reduce Alzheimer’s amyloid-induced mitochondrial dysfunction.
J Alzheimers Dis. 2011;26(3):507-21.

Dragicevic N, Delic V, Cao C, Copes N, Lin X, Mamcarz M, Wang L, Arendash GW, Bradshaw PC.
Caffeine increases mitochondrial function and blocks melatonin signaling to mitochondria in Alzheimer’s mice and cells.
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Esparza TJ, Zhao H, Cirrito JR, Cairns NJ, Bateman RJ, Holtzman DM, Brody DL.
Amyloid-β oligomerization in Alzheimer dementia versus high-pathology controls.
Ann Neurol. 2013 Jan;73(1):104-19.

Ferrie JE, Shipley MJ, Cappuccio FP, Brunner E, Miller MA, Kumari M, Marmot MG.
A prospective study of change in sleep duration: associations with mortality in the Whitehall II cohort.
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He H, Dong W, Huang F.
Anti-amyloidogenic and anti-apoptotic role of melatonin in Alzheimer disease.
Curr Neuropharmacol. 2010 Sep;8(3):211-7.

Suzana Herculano-Houzel
Sleep It Out
Science. 18 October 2013; Vol. 342 no. 6156: pp. 316-317

Huang Y, Potter R, Sigurdson W, Santacruz A, Shih S, Ju YE, Kasten T, Morris JC,
Effects of age and amyloid deposition on Aβ dynamics in the human central nervous system.
Arch Neurol. 2012 Jan;69(1):51-8.

Jáuregui-Barrutia A, Tijero-Merino B, Gómez-Esteban JC, Zarranz JJ.
Sleep disorders in Parkinson’s disease: REM sleep behaviour disorder and restless legs syndrome.
Rev Neurol. 2010 Feb 8;50 Suppl 2:S15-9.

Ju YE, McLeland JS, Toedebusch CD, Xiong C, Fagan AM, Duntley SP, Morris JC, Holtzman DM
Sleep quality and preclinical Alzheimer disease.
JAMA Neurol. 2013 May;70(5):587-93.

Lee JW, Lee YK, Ban JO, Ha TY, Yun YP, Han SB, Oh KW, Hong JT.
Green tea (-)-epigallocatechin-3-gallate inhibits beta-amyloid-induced cognitive dysfunction through modification of secretase activity via inhibition of ERK and NF-kappaB pathways in mice.
J Nutr. 2009 Oct;139(10):1987-93.

Lim AS, Kowgier M, Yu L, Buchman AS, Bennett DA.
Sleep Fragmentation and the Risk of Incident Alzheimer’s Disease and Cognitive Decline in Older Persons.
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Lin L, Huang QX, Yang SS, Chu J, Wang JZ, Tian Q.
Melatonin in Alzheimer’s disease.
Int J Mol Sci. 2013 Jul 12;14(7):14575-93.

Liu XJ, Yuan L, Yang D, Han WN, Li QS, Yang W, Liu QS, Qi JS.
Melatonin protects against amyloid-β-induced impairments of hippocampal LTP and spatial learning in rats.
Synapse. 2013 Sep;67(9):626-36.

Ni C, Tan G, Luo A, Qian M, Tang Y, Zhou Y, Wang J, Li M, Zhang Y, Jia D, Wu C, Guo X.
Melatonin premedication attenuates isoflurane anesthesia-induced β-amyloid generation and cholinergic dysfunction in the hippocampus of aged rats.
Int J Neurosci. 2013 Apr;123(4):213-20.

Rothman SM, Mattson MP.
Sleep disturbances in Alzheimer’s and Parkinson’s diseases.
Neuromolecular Med. 2012 Sep;14(3):194-204.

Taillard J, Philip P, Claustrat B, Capelli A, Coste O, Chaumet G, Sagaspe P.
Time course of neurobehavioral alertness during extended wakefulness in morning- and evening-type healthy sleepers.
Chronobiol Int. 2011 Jul;28(6):520-7.

Tomiyama T.
Involvement of beta-amyloid in the etiology of Alzheimer’s disease
Brain Nerve. 2010 Jul;62(7):691-9.

Emily Underwood
Sleep: The Brain’s Housekeeper?
Science. 18 October 2013; Vol. 342 no. 6156: p. 301

Wyatt JK, Ritz-De Cecco A, Czeisler CA, Dijk DJ.
Circadian temperature and melatonin rhythms, sleep, and neurobehavioral function in humans living on a 20-h day.
Am J Physiol. 1999 Oct;277(4 Pt 2):R1152-63.

Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, O’Donnell J, Christensen DJ, Nicholson C, Iliff JJ, Takano T, Deane R, Nedergaard M.
Sleep drives metabolite clearance from the adult brain.
Science. 2013 Oct 18;342(6156):373-7.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Seeing Eye To Eye?

shopping-decisionsThe world of conflicting information is still doing well, thanks. In the 1950’s, doctors who smoked, smoked Camels. By the 1990’s, many of those doctors had passed away. A few decades back, headlines announced that black pepper caused cancer. Then, miraculously, it didn’t. Conflicting stories about scientific findings abound, even today, and have been the subject of study in an effort to determine the public’s reaction to information that may be harmful or helpful, depending on context (Jensen, 2012). The association of statin drugs and cataracts is a hot topic of recent vintage. The bottom line is evasive because of…conflicting information. It takes only one contrary comment to upset the apple cart of certainty—just one.

The first FDA-approved HMG-CoA reductase inhibitor, or statin, was lovastatin, introduced in 1987. It was, however, found to cause cataracts in beagles if given at high doses, a term that defies definition.  Naturally produced by red yeast rice, certain Aspergillus fungi, and higher fungi such as oyster mushrooms, lovastatin, better known as Mevacor, removes a required building block for cholesterol biosynthesis. Because cholesterol has never been convicted of causing a heart attack (although often accused), there is much wonder these days why statins were ever invented in the first place, since the list of caveats is extensive. But that’s common to most pharmaceuticals, even over-the-counter. Maybe you’ve never noticed, but some brands of OTC meds are more effective than others at treating whatever malady you choose to control. Cough syrup is a good example. The same applies to statins. Some people respond better to some than to others (deVries, 1993).

To indict an inanimate object requires an absolute relation between two events, processes, objects, properties, facts, or states of affairs, where the second event is a consequence of the first. Does owning a swimming pool eventuate a drowning? Does having a throat mean you’ll choke some day? Will you get a ticket every time you speed? Will taking a statin cause you to get a cataract? If you search hard and long, you’re apt to find as many positive as negative correlations to address the last query. For that matter, the same could be said about any human activity or entailment. If you ponder the situation, you might realize that the longer a person lives, the higher the probability of enduring even a minor adversity, including cataracts. Surprisingly, colonoscopy at middle-age has a ten-time higher risk for adverse effect than other commonly used screening tools (Levin, 2006).

Things we learned yesterday differ from ten years ago because of improved measuring techniques and tools, greater understanding of the states of matter and of biological entities, more-user-friendly applications and state-of-the-art materials. In the early 90’s, there was no accurately measureable difference in cataract progression between users and non-users of statin drugs (Chylack, 1993). Almost two decades later, the sophistication of measuring devices has grown considerably enough to track any changes. Something that has been realized along that timeline is the fact that cholesterol is present in the lens of the eye, where its antioxidant effect contributes to lens transparency (Girao, 1999) (Duindam, 1995). There is reasonable speculation that, since statins lower cholesterol levels, there is an increased risk of lens clouding because statins will interfere with the cells responsible for the beneficial process (Leuschen, 2013). Some researchers think that the absence of cholesterol invites lens proteins to move in and take up cholesterol’s space.

The lens is the only part of the body that gets oxygen without blood vessels. It has neither nerves nor connective tissue. Its capsule is made from collagen; its largest mass, from fibers called laminae. Compared to other parts of the eye, the lens has a low energy demand. If they appear, cataracts make the lens opaque. Some opacities are small and require no attention, while others may be large enough to block vision.  For some of us, the proteins in the lens clump together and cloud a small area. This may be the group of statin users (Lai, 2013). Smoking and diabetes hasten this occurrence, although the environment is not totally excused.  Spreading the blame, however, some reports declare systemic drugs like antidepressants, amiodarone, Tamoxifen and nifedipine (a calcium channel blocker known as Procardia) as causative of cataract onset (Lei, 2013).

The number of available statins has grown since their introduction. Their adverse effects are shared, but some are more intense than others, where fluvastatin (Lescol), for example, causes the greatest liver and kidney dysfunction with chronic use (Hippisley, 2010). With this particular drug, its discontinuation returns the risk of cataract to normal within a year.

On the flip side of the coin, an anti-inflammatory portrait of statins has appeared on the scene. Because the cholesterol model of CVD is increasingly viewed with a jaundiced eye in favor of the inflammation model, statins are being touted as the stars of the anti-inflammatory cavalcade. (Truth be told, some culinary/gustatory compounds are better.)  If inflammation increases the risk of cataracts and if statins are anti-inflammatory, then it may be inferred that statins can help to protect against cataract genesis (Gavin, 2000) (Alexios, 2012) (Chodick, 2010)… unless the statins are inhibited by an antibiotic (Schlienger, 2001).

With all this uncertainty, it might pay to take a closer look at statin therapy and to find an alternative.  The naturally-appearing statin in red yeast rice and the other fungi is surrounded by food factors that prevent adverse effects. After all, a statin drug is a chemical isolated from the synergies of foods. Taking a drug provides no excuse to continue behaviors that prompted the drug in the first place, so lifestyle changes might be considered. Cholesterol levels are believed to be minor considerations in cardiovascular health. Besides, who said levels should be lower than 200? Thirty years ago, it was 250. Be careful of what you eat, dump tobacco, take it easy on the ethanol, wear your shades, get enough antioxidants, and listen to your mother.

References

Alexios S Antonopoulos, Marios Margaritis, Regent Lee, Keith Channon, and Charalambos Antoniades
Statins as Anti-Inflammatory Agents in Atherogenesis: Molecular Mechanisms and Lessons from the Recent Clinical Trials
Curr Pharm Des. 2012 April; 18(11): 1519–153

Babizhayev MA, Deyev AI, Yermakova VN, Brikman IV, Bours J.
Lipid peroxidation and cataracts: N-acetylcarnosine as a therapeutic tool to manage age-related cataracts in human and in canine eyes.
Drugs R D. 2004;5(3):125-39.

Chodick G, Heymann AD, Flash S, Kokia E, Shalev V.
Persistence with statins and incident cataract: a population-based historical cohort study.
Ann Epidemiol. 2010 Feb;20(2):136-42.

Chylack LT Jr, Mantell G, Wolfe JK, Friend J, Rosner B.
Lovastatin and the human lens; results of a two year study. The MSDRL Study Group.
Optom Vis Sci. 1993 Nov;70(11):937-43.

de Vries AC, Vermeer MA, Bloemendal H, Cohen LH.
Pravastatin and simvastatin differently inhibit cholesterol biosynthesis in human lens.
Invest Ophthalmol Vis Sci. 1993 Feb;34(2):377-84.

Duindam HJ, Vrensen GF, Otto C, Puppels GJ, Greve J.
New approach to assess the cholesterol distribution in the eye lens: confocal Raman microspectroscopy and filipin cytochemistry.
J Lipid Res. 1995 May;36(5):1139-46.

Gavin J Blake and Paul M R
Are statins anti-inflammatory?
Curr Control Trials Cardiovasc Med. 2000; 1(3): 161–165.

Girao H, Mota C, Pereira
Cholesterol may act as an antioxidant in lens membranes.
Curr Eye Res. 1999 Jun;18(6):448-54.

Hippisley-Cox J, Coupland C.
Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database.
BMJ. 2010 May 20;340:c2197. doi: 10.1136/bmj.c2197.

Jensen JD, Hurley RJ.
Conflicting stories about public scientific controversies: Effects of news convergence and divergence on scientists’ credibility.
Public Underst Sci. 2012 Aug;21(6):689-704.

Lai CL, Shau WY, Chang CH, Chen MF, Lai MS.
Statin Use and Cataract Surgery: A Nationwide Retrospective Cohort Study in Elderly Ethnic Chinese Patients.
Drug Saf. 2013 Jun 15.

Lei JY, Yao K.
Research relating the use of systematic drug and cataracts.
Zhonghua Yan Ke Za Zhi. 2013 May;49(5):468-71.

Leuschen J, Mortensen EM, Frei CR, Mansi EA, Panday V, Mansi I.
Association of Statin Use With Cataracts: A Propensity Score-Matched Analysis.
JAMA Ophthalmol. 2013 Sep 19.

Levin TR, Zhao W, Conell C, Seeff LC, Manninen DL, Shapiro JA, Schulman J.
Complications of colonoscopy in an integrated health care delivery system.
Ann Intern Med. 2006 Dec 19;145(12):880-6.

Mansi IA, Mortensen EM, Pugh MJ, Wegner M, Frei CR.
Incidence of musculoskeletal and neoplastic diseases in patients on statin therapy: results of a retrospective cohort analysis.
Am J Med Sci. 2013 May;345(5):343-8.

Mansi I, Frei CR, Pugh MJ, Makris U, Mortensen EM.
Statins and musculoskeletal conditions, arthropathies, and injuries.
JAMA Intern Med. 2013 Jul 22;173(14):1-10.

Jeanne Mitchell, MS; Richard J. Cenedella, PhD
Human Lens Cholesterol Concentrations in Patients Who Used Lovastatin or Simvastatin
Arch Ophthalmol. 1999;117(5):653-657.

Schlienger RG, Haefeli WE, Jick H, Meier CR.
Risk of cataract in patients treated with statins.
Arch Intern Med. 2001 Sep 10;161(16):2021-6.

Andrew M. Seaman
Statin use tied to cataract development: study
NEW YORK | Thu Sep 19, 2013 4:03pm EDT
http://www.reuters.com/article/2013/09/19/us-statin-cataract-idUSBRE98I11820130919

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Diabetes and CVD: Sometimes You Don’t Want A Sweet Heart

candy-hearts-editJay Cutler, Chicago Bears. Nick Boynton, Blackhawks. Kelli Keuhne, LPGA. Sean Busby, snowboard. Scott Verplank, PGA. Jay Leeuwenburg, NFL. Bobby Clarke, Flyers. Cory Vaughn, Mets (who plays with an insulin pump in his pocket). What do these athletes have in common?  Diabetes. You know, that group of metabolic diseases in which a person has high blood sugar, either because the pancreas can’t make enough insulin, or because cells don’t respond to the insulin that is produced. Frequent urination, increased thirst and a voracious appetite are symptoms.

Type 1 diabetes results from the body’s inability to produce insulin, and means the person has to inject insulin or wear an insulin pump…at least for now. Originally called juvenile diabetes, it can be diagnosed at any age. Type 2 diabetes results from insulin resistance, a state in which cells cannot use insulin the right way. Once in a while there’s an absolute insulin deficiency. This used to be called adult-onset diabetes. Gestational diabetes may be the third type, affecting pregnant women without a prior diagnosis who develop a high glucose level. This could lead to type 2.

Diabetes is bad enough, but the complications, especially if the diabetes is untreated, can be a nightmare. If the cardiovascular system is involved—and it often is—it’ll be worse than a nightmare. It might take ten or twenty years, but one complication or another is likely to pop up. In fact, a person might experience the complication before he even knows he has diabetes. Atherosclerosis, angina, heart attack, stroke and peripheral artery disease are not uncommon. But then there is damage to the smallest blood vessels, the capillaries. This microvascular affliction can lead to blindness and can cause scarring changes in kidney tissue. Diabetic neuropathy causes numbness, tingling and pain, especially in the feet, perhaps leading to amputation. Cognitive function is at risk, too. In the heart, small vessel disease is called cardiac syndrome X, non-obstructive coronary disease or microvascular angina, all names for microangiopathy.

The upper threshold of fasting glucose has been lowered from 140 to125 mg/dL. The upper threshold for normal glycemia has also been reduced, from 115 to 110 mg/dL. A fasting glucose of 110 to 125 mg/dL is now classified as impaired fasting glucose (IFG). Today, from the perspective of a cardiologist, diabetes is a cardiovascular disease (Grundy, 1999). The sad fact is that about sixty-five percent of people with diabetes die from heart disease and stroke. What happens is that sugar actually coats red blood cells, making them stiff and sticky and interfering with blood flow. That can cause a plaque to develop on the wall of an artery. At the same time, levels of the powerful vasodilator, nitric oxide, drop significantly, which raises blood pressure. After all this, the CVD risk for men with diabetes is twice that of men without; for women it’s three times (Howard, 2000). Nasty business, this diabetes stuff, but what can we do to control it?  We would like to see you lose that thing hanging over your belt. A half hour a day of brisk walking will help you do that. Reduce salt and sugar consumption and stick with lean proteins, which can include meat and especially fish. And you don’t want to smoke.

Atherosclerosis is now treated as an inflammatory disease, not purely a cholesterol-driven one (Libby, 2005). Diabetes is a contributor to that inflammation, which may also affect cognitive function (Beilharz, 2013). But there are dietary interventions that offer promise in diabetes management. In a double-blinded and placebo-controlled Chinese trial, subjects with type 2 diabetes were fed agaricus mushrooms as part of their treatment regimen. After twelve weeks, their insulin resistance improved (Hsu, 2007). In some foods where the amino acid lysine is structurally bound to protein, we find alpha lipoic acid, a sulfur-based anti-oxidant enzyme. Kidney, heart, liver, spinach, broccoli and yeast extracts are the better food sources, but contain too little to have a significant physiological effect. Amounts are more reliable in a supplement, and have been found to improve glucose status in both lean and obese patients, using 400 mg twice a day for a month (Konrad, 1999). Glucose disposal is the rate at which glucose is taken from the blood by peripheral tissue, increases of which are desirable. Alpha lipoic acid enhances that activity while simultaneously addressing diabetic neuropathy issues (Jacob, 1995, 1996, 1999).

In the olden days, we used to call it roughage. Today, it’s what it is—fiber. Every part of a plant we can’t digest fits the description. Fiber passes through the GI tract relatively intact. The soluble kind dissolves in water to form a gel, which can help to lower cholesterol and glucose. Oats, peas and beans, apples, citrus, carrots, barley and psyllium are examples. The insoluble kind moves stuff through the GI system until it gets to the exit. Whole wheat flour and bran, nuts, beans, cauliflower fit the category. Both kinds are beneficial in helping to prevent sickness, but psyllium (as in Metamucil®) can be taken from the spoon in water or juice, and is safe, well-tolerated, and improves blood glucose and serum lipids (Anderson, 1999) (Pastors, 1991). It also can be mixed into a meal (Wolever, 1991).

It isn’t easy to eat broccoli every day to get the chromium that’s been found to control blood sugar. What’s more, agricultural and manufacturing practices can affect content of the mineral, so supplements have been made available. Surprisingly, in a study performed at the U of TX, chromium not only tamed glucose response in diabetes patients, but also lowered triglyceride levels by seventeen percent after two months’ supplementation of the picolinate form (Lee, 1994). Combined with biotin, this mineral has proved itself a valuable tool in the diabetes management armamentarium (Singer, 2006). Recent meta-analysis hammers the point home (Abdollahi, 2013).

Need more? Magnesium intake is inversely associated with diabetes risk, even in groups with bad habits and a family history of disease (Lopez-Ridaura, 2004), and it provides greater insulin sensitivity (Fung, 2003) to lower the risk of developing type 2. Maybe what comes out of a person’s mouth is what defiles him in the view of others, but what goes in can sully the whole machine from the hidden side. Eating well is more than just a magazine title.

References

Abdollahi M, Farshchi A, Nikfar S, Seyedifar M.
Effect of chromium on glucose and lipid profiles in patients with type 2 diabetes; a meta-analysis review of randomized trials.
J Pharm Pharm Sci. 2013;16(1):99-114.

Anderson JW, Allgood LD, Turner J, Oeltgen PR, Daggy BP.
Effects of psyllium on glucose and serum lipid responses in men with type 2 diabetes and hypercholesterolemia.
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Anderson RA, Cheng N, Bryden NA, Polansky MM, Cheng N, Chi J, Feng J.
Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes.
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Short exposure to a diet rich in both fat and sugar or sugar alone impairs place, but not object recognition memory in rats.
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*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Blood Pressure and…

bloodpressure-cuffThere is no naturally normal value for blood pressure (BP), but if yours is higher than that level deemed risky, you need to do something about it or face the possibility of some nasty consequences, such as stroke or cardiac episode, both of which can kill you—and are preventable. During each beat of the heart, pressure varies between a maximum, called systolic, and a minimum, called diastolic. The systolic pressure is the force that pushes blood out of the left ventricle; diastolic pressure refers to the heart at rest. The word diastole means dilation.

High blood pressure can cause arteries to become harder and thicker. Sometimes that can cause a bulge, an aneurysm, a weak spot in the artery that is subject to rupture, resulting in hemorrhage and probably death. Aneurysms don’t disappear by themselves, so some kind of invasive procedure might follow, depending on size and location. Copper deficiency is associated with aneurysm risk, so you might want to look at your diet, particularly if it’s high in zinc, the element some believe will improve male health and performance. But assuring copper sufficiency won’t necessarily prevent an aneurysm caused by elevated BP.

If the heart has to work harder to pump blood against the elevated pressures in the vessels, the heart muscle can get thicker, which makes it even more difficult to pump blood. This is the onset of heart failure, which may or may not be easily treated. In fortunate instances, a thickened heart can revert to normal size. Effects of continued high BP may involve the kidneys, brain and eyes. In polls, most people would rather die than face blindness (Giridhar, 2002) (Pfizer, 2008), which can result from hypertensive retinopathy.

There is no known cause of essential hypertension, but risks have been identified to include salt intake, obesity, race, physical activity, stress, heredity and diet. Secondary hypertension may be related to kidney, endocrine or neurological dysfunction. Medications, such as amphetamines and decongestants, can elevate blood pressure, as can alcohol. What is termed “normal” BP is a systolic pressure less than 120 mmHg and a diastolic pressure less than 80 mmHg (120/80). It takes a visit with your physician to determine your personal baseline and to work out a protocol if one is deemed necessary. That might include a medication besides a dietary intervention to address overweight.

Because cardiovascular disease is a leading cause of mortality in the economically developed world, much attention has been given to it. Diet and lifestyle are significant influences on cardiac risk, and may instigate abnormal lipid profiles, insulin resistance, diabetes and other pathologies suggestive of their impact. Of interest in the management of CVD risk factors are omega-3 fatty acids. Both omega-3 and omega-6 fats are considered essential; the body is unable to synthesize them. The conversion of the mother omega-3 and omega-6 fats, alpha-linolenic acid and linoleic acid, to longer-chain fatty acids, EPA/DHA and arachidonic acid, is terribly inefficient. Because omega-6 fats are held to be a dietary excess by virtue of a regimen high in processed foods and cheap supermarket oils, omega-3 fats, as fish oil, have received considerable interest. Fish oil is rich in EPA and DHA, the former having cardiovascular attributes and the latter having cerebral and retinal activity. Together, these fatty acids have induced moderate reductions in blood pressure at doses approximating 3 grams a day in both treated and untreated persons with elevated BP (Abeywardena, 2011). The mechanism explaining the activity is uncertain, but appears related to improvement in vascular endothelial function, one of these being reduction in stiffness. To address concerns about fish oil’s effect on LDL cholesterol, it is noted that the change in LDL particle size from small to large is a benefit (Ibid.).

One characteristic of hypertension is thickening of the arterial wall. In an animal model of hypertension, arterial thickening was attenuated with DHA treatment and the blood pressure decrease was compared to that induced by a beta blocker. Though only conjectural, other mechanisms by which fish oil lowers BP may involve activation of potassium channels (Toshinori, 2013). It is also possible that the anti-inflammatory compounds encouraged by fish oils ameliorate BP through a hormone-like effect that works in conjunction with the fatty acids’ blood-thinning character. Doses here approach 3 grams a day (Cabo, 2012).

In a twelve-week comparison/contrast trial pitting the omega-6 safflower oil against fish oil, the latter was found to offer significant benefit in reducing blood pressure in subjects with mild hypertension (Radack, 1991), while introducing no adverse changes in plasma lipid values. Including this with sixty-nine other random trials, researchers agree that available evidence indicates that inclusion of EPA/DHA in one’s diet reduces both systolic and diastolic BP at doses of at least 2 grams a day (Miller, 2014). Joining a fish oil protocol with a weight loss program, where applicable, wrought a 13 point drop in systolic and a 9 point drop in diastolic numbers in a cohort having a body mass index in excess of 31.0, the point at which obesity is defined (Bao, 1998).

If you take a prescription medication to keep your blood pressure controlled, don’t just stop it in favor of the fatty acids in fish oil. Doing so risks damage from BP rebound, which can cause serious damage to an artery. If you experience unwelcome side effects from your meds, talk with the doctor and look for an alternative drug. There certainly are enough of them on the market. Integrating fish oil with a BP drug is not generally a hazard, and may even be a boon. On the other hand, if BP falls too low, you can get dizzy, especially after standing from a sitting position. Essential fatty acids exist in the realm of complementary medicine, which is meant to complement, not necessarily to replace, conventional modalities in treating a variety of physical maladies. Hypertension is one that is relatively easy to manage.

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Cicero AF, Ertek S, Borghi C.
Omega-3 polyunsaturated fatty acids: their potential role in blood pressure prevention and management.
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Long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and blood pressure: a meta-analysis of randomized controlled trials.
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Toshinori Hoshia, Bianka Wissuwab, Yutao Tiana, Nobuyoshi Tajimaa, Rong Xua, Michael Bauerb, Stefan H. Heinemannc, and Shangwei Houd
Omega-3 fatty acids lower blood pressure by directly activating large-conductance Ca2+-dependent K+ channels
PNAS March 4, 2013. Published online before print March 4, 2013

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Understanding the Highs and Lows of Triglycerides

Triglycerides-choiceYou have triglycerides. So do we. Sometimes a lot, sometimes not, sometimes too many. They’re formed by combining glycerol with three molecules of fatty acid, which can be the same or different. Glycerol is a sugar alcohol that provides the backbone of many lipids. It’s an important intermediate in carbohydrate and fat metabolism. High levels of triglycerides have been linked to atherosclerosis and heart disease. They’re the natural molecular form that makes up virtually all fats and oils in both plants and animals. Most of us know our cholesterol levels, and we even know about the differences between HDL and LDL. But managing triglycerides (TG’s) is just as important to cardiac health. About a third of U.S. adults have borderline TG levels, between 150 and 199 milligrams per deciliter. Many of those with high TG’s are older whites who smoke, are overweight, and who get less than 150 minutes of exercise a week. Women have a lower risk than men, and blacks and Mexican Americans have even lower risks (Ford, 2009).

The body makes TG’s from carbohydrates and sends them to fat cells where they’re stored for energy. High TG levels often accompany low HDL, in a kind of lipid profile that may run in families. HDL cholesterol between 40 and 60 milligrams per deciliter, and LDL less than 100 are reasonable goals. Where TG’s store unused calories and provide energy, cholesterol is used to build cells and to make some hormones. Really high TG’s can be a sign that something else is amiss, like high blood pressure or high blood glucose. Low thyroid hormones, liver or kidney conditions, and some genetic missteps can affect how the body converts fat to energy, so TG readings will be elevated. But beta blockers taken for high blood pressure, some diuretics, steroids and birth control pills can raise TG levels, too.

Lifestyle changes are the first line of defense against high TG’s. Losing weight, cutting calories and avoiding excess sugars and refined foods are simple steps, although weight loss may initially be a challenge. It takes only a few pounds to make a difference, and light exercise and alcohol avoidance can help. But there is a supplement that can rescue high TG’s—fish oil. Of course, when Big Pharma realized this, they had to make a prescription form—Lovaza, Glaxo Smith-Kline’s omega-3 prescription. What makes it different from plain fish oil is the FDA’s blessing, which states that Lovaza is the only omega-3 medication so approved. No other fish oil product may be called a medication. The same effect, though, can be realized by taking multiple capsules of OTC product. But because one’s prescription plan pays for Lovaza, it’s cheaper for the patient…and GSK makes a ton of money.

Fish oil contains EPA and DHA, fatty acids that benefit the cardiovascular system and the eyes and brain, respectively. The fatty acids from fish oils are anti-inflammatory and anti-thrombotic; they compete successfully with substances that cause platelet aggregation and vasoconstriction. In hypertriglyceridemia, fish oil decreases the secretion of very low density lipoproteins (VLDL), increases VLDL clearance and reduces TG transport (Nestel, 2000) (Stark, 2000). It is held that fish oil can influence CVD risk factors to such an extent as to reduce risk of coronary heart disease by as much as twenty-seven percent (Stark, 2000).

Some products labeled as fish oil are not really oils at all, but rather alternate lipids known as fatty acid ethyl esters, differing from authentic fish oil triglycerides. Because free fatty acids are rapidly oxidized, the TG structure offers greater stability to the fatty acids and prevents breakdown and oxidation (Segura, 1988). Ethyl esters are derived from the reaction of free fatty acids with ethanol. Here, the glycerol backbone of the TG is removed and substituted with alcohol (Mogelson, 1984). The resulting ester allows for fractional distillation of the long-chain fatty acids at lower temperatures. At this point, the EPA and DHA can be manipulated to levels greater than those found in the fish (Saghir, 1997). Ethyl esters (EE’s) are uncommon in nature, so are not properly digested and absorbed by the body. The process can be reversed by using food grade enzymes, restoring the product to its rightful TG form with the glycerol backbone. Doing this is not common to the industry because of the cost. The fatty acid-ethanol bond is about fifty times more resistant to digestive enzymes (pancreatic lipase) as compared to the triglyceride form (Yang, 1990) (Yang, 1990). TG fish oil yields fifty percent more plasma EPA/DHA after absorption than the EE form (Beckerman, 1990) (Dyerberg, 2010). Over the long term, however, EE absorption seems to equal out after a few months’ intake (Sadovsky, 2009). It is conjectured that the slower activity of EE fish oil results in sustained inhibition of sodium and calcium channels, helping to prevent arrhythmia (Leaf, 2003) (Lavie, 2009).

There is no discernible health risk to EE fish oil, not even for a person sensitiveto alcohol. There are stories about EE being able to melt polystyrene. Alcoholand water are polar substances, having different electrical charges at oppositeends. They do not react with non-polar materials, such as Styrofoam. So, if you’veever heard that EE fish oil will dissolve a Styrofoam cup, dismiss the thought.When it comes to oxidation, though, EE will oxidize faster than the TG fish oil,making it less reliable (Song, 1997). The TG fish oil is naturally occurringand less likely to go rancid. Doubtless there are myriad studies to support andnegate the efficacy of each form, but if either one lowers your triglyceridelevels, there’s no debate.

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*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Chocolate Covered Prevention

dark-chocolateChocolate consumption can reduce cardiac risk by a third, according to a very recent pronouncement based on meta-analyses of previous works.  Scientists report that chocolate could be a viable factor in the reduction of heart disease and metabolic syndrome by virtue of its polyphenol content, keeping company with fruits and vegetables, extra virgin olive oil, wine and teas.  The scientists who offered this report were careful to note that none of the seven trials that were examined had followed all the hallmarks of the scientific protocol, including control and randomization, meaning that a control group / trial group selection was not done to eliminate bias in treatment.  On the other hand, empirical results were used to support the hypotheses.

Although he commented that additional, randomized and controlled studies are needed to ascertain these results, lead scientist, Oscar Franco, working at England’s Cambridge University, said that, “…levels of chocolate consumption seem to be associated with a substantial reduction in the risk of cardiometabolic disorders.”  After looking carefully at more than one hundred thousand study participants and examining their risks for CVD, diabetes, stroke and metabolic syndrome, Franco and his group noted that, “The highest levels of chocolate consumption were associated with a 37% reduction in cardiovascular disease…and a 29% reduction in stroke compared with the lowest levels.”   Based on these observations, levels of chocolate consumption seem to be associated with a substantial reduction in the risk of cardiometabolic disorders.

This is not the first study to compliment chocolate for its inherent character, but it does make the loudest presentation.   It’s the polyphenols in cocoa that are the heroes, a class of compounds that includes the bioflavonoids (of which there are a few thousand), lignins, and tannins.   The flavonoids in chocolate comprise the highest concentration among commonly consumed foods—more than ten percent of the weight of cocoa powder.  Among them, catechin and epicatechin, two of the procyanidin flavonoids, are among the most abundant, and are also found in tea.  These flavonoids oppose free radical injury because of their antioxidant effect, but also have been found to lower total cholesterol, to reduce blood pressure, to inhibit sticky platelets, and to improve blood flow to vital organs.  (Pryde. 2011)  One anti-hypertensive attribute of cocoa is the activation of nitric oxide, a gas that occurs in the body naturally, which is released from vascular epithelial cells to inhibit muscular contraction and thereby induce relaxation of blood vessels.  (Corti. 2009)  (Buijsse. 2010)

Flavonoids exist in all plant foods, where they shield a plant from environmental insults and offer the means to repair damage.  When we consume these plants, the benefit passes to us, including the capability to resist oxidative damage from things like cigarette smoke, vehicular and factory discharge, and poor dietary choices.  Some chocolate flavonoids may be lost to processing, but manufacturers are looking to control that.

Research at Harvard Medical School looked more closely at subclinical coronary disease and diet, finding an inverse relationship between calcified plaque and chocolate consumption.  (Djousse. 2011)  Those who consumed dark chocolate—never milk chocolate—once or twice a week (about an ounce at a time) demonstrated a greater positive result than those who consumed it less than three times a month.  The inclusion of chocolate in so stellar a group as green tea and soy as contributors to heart health is no small feat, considering that chocolate is more of a snack food than part of a meal.  That it was seen to lower diastolic blood pressure as well as systolic is a feather in its cap.  (Hooper. 2008)

We have to keep in mind that chocolate is relatively high in lipids, which means it’s high in calories.  The saturated stearic acid constitutes one-third of the fats in cocoa butter, but has zero influence on cholesterolemic response.  Another one-third fat fraction in cocoa is oleic acid, a heart-healthy monounsaturated fat, followed by the last third, palmitic acid, which is saturated but self-limiting, even though it is the first fatty acid produced during lipogenesis (the synthesis of fatty acids by the body).  In the presence of linoleic acid (an omega-6) at 4.5% of calories (~90 calories), palmitic acid has no effect on cholesterol levels.  (French. 2002)  So, the calories in chocolate can be healthy. But we must be reminded not to have too much of a good thing.

References

Adriana Buitrago-Lopez, Jean Sanderson, Laura Johnson, Samantha Warnakula, Angela Wood, Emanuele Di Angelantonio, Oscar H Franco
Chocolate consumption and cardiometabolic disorders: systematic review and meta-analysis
BMJ 2011; 343:d4488 doi: 10.1136/bmj.d4488 (Published 29 August 2011)

Moira McAllister Pryde and William Bernard Kannel
Efficacy of Dietary Behavior Modification for Preserving Cardiovascular Health and Longevity
Cardiol Res Pract. 2011; 2011: 820457.

Corti R, Flammer AJ, Hollenberg NK, Lüscher TF
Cocoa and cardiovascular health.
Circulation. 2009 Mar 17;119(10):1433-41.

Buijsse B, Weikert C, Drogan D, Bergmann M, Boeing H.
Chocolate consumption in relation to blood pressure and risk of cardiovascular disease in German adults.
Eur Heart J. 2010 Jul;31(13):1616-23.

Djoussé L, Hopkins PN, North KE, Pankow JS, Arnett DK, Ellison RC.
Chocolate consumption is inversely associated with prevalent coronary heart disease: the National Heart, Lung, and Blood Institute Family Heart Study.
Clin Nutr. 2011 Apr;30(2):182-7.

Djoussé L, Hopkins PN, Arnett DK, Pankow JS, Borecki I, North KE, Curtis Ellison R.
Chocolate consumption is inversely associated with calcified atherosclerotic plaque in the coronary arteries: the NHLBI Family Heart Study.
Clin Nutr. 2011 Feb;30(1):38-43.

Hooper L, Kroon PA, Rimm EB, Cohn JS, Harvey I, Le Cornu KA, Ryder JJ, Hall WL, Cassidy A.
Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials.
Am J Clin Nutr. 2008 Jul;88(1):38-50.

French MA, Sundram K, Clandinin MT.
Cholesterolaemic effect of palmitic acid in relation to other dietary fatty acids.
Asia Pac J Clin Nutr. 2002;11 Suppl 7:S401-7.

Steinberg FM, Bearden MM, Keen CL.
Cocoa and chocolate flavonoids: implications for cardiovascular health.
J Am Diet Assoc. 2003 Feb;103(2):215-23.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.