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Probiotics and Blood Pressure

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Maybe what happens in Las Vegas stays in Las Vegas, but what happens in your gut doesn’t stay in your gut, the place we think of as the processing plant that makes nutrients available for use by the body and wastes available for disposal. That part’s correct, but recent interest in the machinations of the system has researchers looking at its relationship to the brain. That means that some of what happens in the gut goes to your head and bypasses the enteric nervous system (ENS), that part of the body called the second brain. Working autonomously, the enteric nervous system is able to coordinate reflexes while controlling the gastrointestinal activity upon which humans rely. Although it communicates with the brain by way of the vagus nerve, the ENS can work independently through a series of neurons that control peristalsis (churning of intestinal contents) and monitor mechanical, chemical and electrical conditions within the system, such as those involved in enzyme secretion and neurotransmitter manufacture. The neurotransmitters of the gut are the same as those in the central nervous system (CNS): acetylcholine, dopamine and serotonin. In fact, more than ninety percent of the body’s serotonin lies in the gut, where it modulates cells of the immune system (Sepiashvili, 2013) (Mawe, 2013). That’s uncommon knowledge, for sure.

What’s this got to do with the brain? Using functional magnetic resonance imaging (fMRI), scientists at UCLA Medical School found that women who regularly consumed probiotic-rich yogurt showed altered activity of brain regions that control the processing of emotion and sensation. The lead author, Dr. Kirsten Tillisch, M.D., commented that the study is of singular merit because it’s the first to show an interaction between a probiotic and the brain. In this work, healthy women with no GI or psychiatric symptoms ate fermented yogurt containing Bifido-, Lacto-, and Strepto- bacterial strains twice a day for a month, and were compared/contrasted to groups that either abstained from such a dairy product or ate one lacking fermented cultures. Before-and-after fMRI’s measured resting brain activity and brain responses to emotion-recognition tasks. Those are the kind in which you look at an image and determine a person’s mood by his facial expressions. This avenue was taken because a previous relationship between gut flora and affective behavior was realized (Umu, 2013) (Dinan, 2013) (Gomborone, 1993) (Robertson, 1989).

Dr. Tillisch observed brain effects in several areas, including those involved in sensory processing and emotional response. An additional conclusion, practically foregone, is that gut flora composition is directed by what we eat (Tillisch, 2013). It is widely accepted that relatively high fiber diets create a gut environment different from typical Western diets. If the brain can send signals to the gut that make you nauseous in times of mental stress, why can’t the gut send messages to the brain?  Inspection has found that Lactobacillus rhamnosus bacteria, common to many yogurt products, affect GABA levels in the brain (Bravo, 2011). GABA is an inhibitory neurotransmitter that reduces anxiety and depression-related behavior. Whether or not Dr. Tillisch’s work is preliminary to something more definitive makes little difference because interest in this field had been piqued years ago (Robertson, 1989).

Some areas of medical and functional study are rife for contrivance, either of outcomes or numbers or some other elements of scientific reporting. The study of autism and its related spectrum of anomalies are not excused from academic chicanery. However, the gut-brain nexus in the study of cerebral challenges offers a fertile arena for probiotic-central nervous system exploration. That there exist perturbations in the gut flora of autistic individuals is properly recognized (Parracho, 2005) (Finegold, 2002). Moving on this link, researchers have identified the higher levels of “bad bacteria” in the guts of children with autism as a variety of Clostridia, though not necessarily defining a cause-effect relationship, but only an association (Pilcher, 2004). Admittedly, genetic and environmental factors play a role in the etiology of this condition. Nonetheless, it is speculated, with at least a small certainty, that probiotics might allay some symptoms of autism by attenuating the toxic by-products of these ignoble bacteria strains.

Anxiety and depression are comorbidities of functional bowel disorders. In subjects so affected, discordant alterations in GABA receptors were remediated by the administration of Lactobacillus rhamnosus, highlighting the valuable role of bacteria in the bi-directional communication of the gut-brain axis (Bravo, 2011) and hinting that certain micro-organisms can be used to treat stress-related disorders, such as anxiety and depression (Cryan, 2012 and 2011).

A venture into neurogastroenterology is as labyrinthine an exercise as can be imagined, right up there with the Biblical epiphany of being fearfully and wonderfully made, and has prompted a convention of “experts” called the International Scientific Association for Probiotics and Prebiotics (ISAPP). Available data on the role of gut bacteria in brain function ascertain the interaction of this microbiota with the ENS, the CNS, and the neuroendocrine and neuroimmune systems. Mammalian brain development and subsequent adult behavior are likewise affected. This could account for the behavioral abnormalities that occasionally accompany gastrointestinal ailments such as IBS and Crohn’s disease, aside from their discomfort.

Short-chain fatty acids are made in the colon when dietary fiber is fermented. These acids contribute to the integrity of the immune and digestive systems, and to the regulation of intestinal (and other) inflammation (Smith, 2013), but their overexpression can be hazardous to cerebral health because they deplete inhibitory GABA (El-Ansary, 2011). Propionic acid (PA) is the main player in this cranial drama, inciting autistic features (El-Ansary, 2012) by increasing markers of oxidative stress, including lipid peroxidation and concomitant decreases in glutathione. Lactic acid bacteria ameliorate the state by increasing GABA stores, (Bravo, 2011) even in the presence of PA, by virtue of their psychoactive character (Perez-Burgos, 2013). And they control PA production by sequestering the Clostridia responsible for its appearance in the first place.

The potential of gut microflora to fine tune human physiology goes beyond the digestive, cardiovascular and immune systems, now to include the nervous system. The thought of regulating cognitions, behaviors, sensations and emotions with bacteria is more than just enlightening.

References

Aihara K, Kajimoto O, Hirata H, Takahashi R, Nakamura Y.
Effect of powdered fermented milk with Lactobacillus helveticus on subjects with high-normal blood pressure or mild hypertension.
J Am Coll Nutr. 2005 Aug;24(4):257-65.

Aleixandre A, Miguel M, Muguerza B.
Peptides with antihypertensive activity from milk and egg proteins.
Nutr Hosp. 2008 Jul-Aug;23(4):313-8.

Boelsma E, Kloek J.
Lactotripeptides and antihypertensive effects: a critical review.
Br J Nutr. 2009 Mar;101(6):776-86.

Javier A. Bravo, Paul Forsythe, Marianne V. Chew, Emily Escaravage, Hélène M. Savignac, Timothy G. Dinan, John Bienenstock, John F. Cryan
Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve
PNAS. September 20, 2011; vol. 108 no. 38: 16050-16055

Geraldine O. Canny and Beth A. McCormick
Bacteria in the Intestine, Helpful Residents or Enemies from Within?
Infect. Immun. August 2008 vol. 76 no. 8 3360-3373

Cicero AF, Rosticci M, Veronesi M, Bacchelli S, Strocchi E, Melegari C, Grandi E, Borghi C.
Hemodynamic effects of lactotripeptides from casein hydrolysate in Mediterranean normotensive subjects and patients with high-normal blood pressure: a randomized, double-blind, crossover clinical trial.
J Med Food. 2010 Dec;13(6):1363-8.

Cremonesi P, Chessa S, Castiglioni B.
Genome sequence and analysis of Lactobacillus helveticus.
Front Microbiol. 2013 Jan 11;3:435.

Ehlers PI, Kivimäki AS, Turpeinen AM, Korpela R, Vapaatalo H.
High blood pressure-lowering and vasoprotective effects of milk products in experimental hypertension.
Br J Nutr. 2011 Nov;106(9):1353-63.

Gonzalez-Gonzalez C, Gibson T, Jauregi P.
Novel probiotic-fermented milk with angiotensin I-converting enzyme inhibitory peptides produced by Bifidobacterium bifidum MF 20/5.
Int J Food Microbiol. 2013 Oct 15;167(2):131-7.

Jauhiainen T, Vapaatalo H, Poussa T, Kyrönpalo S, Rasmussen M, Korpela R
Lactobacillus helveticus fermented milk lowers blood pressure in hypertensive subjects in 24-h ambulatory blood pressure measurement.
Am J Hypertens. 2005 Dec;18(12 Pt 1):1600-5.

Lye HS, Kuan CY, Ewe JA, Fung WY, Liong MT.
The improvement of hypertension by probiotics: effects on cholesterol, diabetes, renin, and phytoestrogens.
Int J Mol Sci. 2009 Aug 27;10(9):3755-75.

Minervini F, Algaron F, Rizzello CG, Fox PF, Monnet V, Gobbetti M.
Angiotensin I-converting-enzyme-inhibitory and antibacterial peptides from Lactobacillus helveticus PR4 proteinase-hydrolyzed caseins of milk from six species.
Appl Environ Microbiol. 2003 Sep;69(9):5297-305.

O’Hara AM, Shanahan F.
The gut flora as a forgotten organ.
EMBO Rep. 2006 Jul;7(7):688-93.

Seppo L, Jauhiainen T, Poussa T, Korpela R.
A fermented milk high in bioactive peptides has a blood pressure-lowering effect in hypertensive subjects.
Am J Clin Nutr. 2003 Feb;77(2):326-30.

Kirsten Tillisch, Jennifer Labus, Lisa Kilpatrick, Zhiguo Jiang, Jean Stains, Bahar Ebrat, Denis Guyonnet, Sophie Legrain–Raspaud, Beatrice Trotin, Bruce Naliboff, Emeran A. Mayer
Consumption of Fermented Milk Product With Probiotic Modulates Brain Activity
Gastroenterology.

June 2013; Volume 144, Issue 7: 1394-1401.e4

Tuomilehto J, Lindström J, Hyyrynen J, Korpela R, Karhunen ML, Mikkola L, Jauhiainen T, Seppo L, Nissinen A.
Effect of ingesting sour milk fermented using Lactobacillus helveticus bacteria producing tripeptides on blood pressure in subjects with mild hypertension.
J Hum Hypertens. 2004 Nov;18(11):795-802.

Verna EC, Lucak S.
Use of probiotics in gastrointestinal disorders: what to recommend?
Therap Adv Gastroenterol. 2010 Sep;3(5):307-19.

Yamamoto N, Takano T.
Antihypertensive peptides derived from milk proteins.
Nahrung. 1999 Jun;43(3):159-64.

*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.

References

Abeywardena MY, Patten GS.
Role of ω3 long-chain polyunsaturated fatty acids in reducing cardio-metabolic risk factors.
Endocr Metab Immune Disord Drug Targets. 2011 Sep 1;11(3):232-46.

Bao DQ, Mori TA, Burke V, Puddey IB, Beilin LJ.
Effects of dietary fish and weight reduction on ambulatory blood pressure in overweight hypertensives.
Hypertension. 1998 Oct;32(4):710-7.

Biermann J, Herrmann W.
Modification of selected lipoproteins and blood pressure by different dosages of n-3-fatty acids.
Z Gesamte Inn Med. 1990 Sep 15;45(18):540-4.

Borghi C, Cicero AF.
Omega-3 polyunsaturated fatty acids: Their potential role in blood pressure prevention and management.
Heart Int. 2006;2(2):98.

Cabo J, Alonso R, Mata P.
Omega-3 fatty acids and blood pressure.
Br J Nutr. 2012 Jun;107 Suppl 2:S195-200.

Cicero AF, Ertek S, Borghi C.
Omega-3 polyunsaturated fatty acids: their potential role in blood pressure prevention and management.
Curr Vasc Pharmacol. 2009 Jul;7(3):330-7.

Margolin G, Huster G, Glueck CJ, Speirs J, Vandegrift J, Illig E, Wu J, Streicher P, Tracy T.
Blood pressure lowering in elderly subjects: a double-blind crossover study of omega-3 and omega-6 fatty acids.
Am J Clin Nutr. 1991 Feb;53(2):562-72.

Miller PE, Van Elswyk M2, Alexander DD3.
Long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and blood pressure: a meta-analysis of randomized controlled trials.
Am J Hypertens. 2014 Jul;27(7):885-96.

Mori TA.
Omega-3 fatty acids and blood pressure.
Cell Mol Biol (Noisy-le-grand). 2010 Feb 25;56(1):83-92.

Morris MC, Taylor JO, Stampfer MJ, Rosner B, Sacks FM.
The effect of fish oil on blood pressure in mild hypertensive subjects: a randomized crossover trial.
Am J Clin Nutr. 1993 Jan;57(1):59-64.

Radack K, Deck C, Huster G.
Arch Intern Med. 1991 Jun;151(6):1173-80.
The effects of low doses of n-3 fatty acid supplementation on blood pressure in hypertensive subjects. A randomized controlled trial.

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.

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.