Control of heart function

The cardiovascular system circulates blood throughout the body to supply oxygen and nutrients and to remove waste products. Each time the heart beats, blood is pumped out of the heart and into the body to supply oxygen to working muscles, or to the lungs for re-oxygenation. Heart rate refers to the number of times the heart beats per minute, and is directly related to the workload being placed on the heart. 

Control of the heart's functioning is highly complex. The heart's internal electrical system controls the timing of heartbeat by regulating the heart rate and heart rhythm and aims to maintain a steady heart rate under all conditions. Other parts of the body send multiple, interacting signals for the heart to beat either faster or slower in order to respond to the rapidly changing requirements of the body.

These signals emanate from or are influenced by:

• body’s energy level, oxygen state and temperature
• physical load,
• autonomic nervous system,
• level of oxidative stress,
• epigenetic factors (activation / inactivation of genes that control the heart),
• levels of circulating neuro- and gasotransmitters (dopamine, noradrenaline, nitric oxide), and
• the hormonal system.

References

Variables influencing heart rate. Prog Cardiovasc Dis. Jul-Aug 2009;52(1):11-9. https://pubmed.ncbi.nlm.nih.gov/19615488/

Autonomic and endocrine control of cardiovascular function. World J Cardiol. 2015 Apr 26; 7(4): 204–214. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404375/

Cardiovascular Consequences of Cortisol Excess. Vasc Health Risk Manag. 2005 Dec; 1(4): 291–299. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1993964/

Effects of urinary cortisol levels and resting heart rate on the risk for fatal and nonfatal cardiovascular events. Atherosclerosis, Volume 248, May 2016, Pages 44-50. https://www.sciencedirect.com/science/article/pii/S0021915016300739

Correlation Between Striatal Dopamine D2/D3 Receptor Binding and Cardiovascular Activity in Healthy Subjects. American Journal of Hypertension, Volume 19, Issue 9, September 2006, Pages 964–969. https://academic.oup.com/ajh/article/19/9/964/146323

The epigenetic landscape related to reactive oxygen species formation in the cardiovascular system. Br J Pharmacol. 2017 Jun; 174(12): 1533–1554. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446579/

The cardiac sympathetic co-transmitter neuropeptide Y is pro-arrhythmic following ST-elevation myocardial infarction despite beta-blockade. European Heart Journal, Volume 41, Issue 23, 14 June 2020. https://academic.oup.com/eurheartj/article/41/23/2168/5675548

The Role of Neuropeptide Y in Cardiovascular Health and Disease. Front Physiol. 2018; 9: 1281. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157311/

Heat Stress and Cardiovascular, Hormonal, and Heat Shock Proteins in Humans. J Athl Train. 2012 Mar-Apr; 47(2): 184–190. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3418130/

Stress (heat shock) proteins: molecular chaperones in cardiovascular biology and disease. Circ Res. 1998 Jul 27;83(2):117-32. https://pubmed.ncbi.nlm.nih.gov/9686751/

Mammalian γ2 AMPK regulates intrinsic heart rate. Nat Commun. 2017 Nov 2;8(1):1258. https://pubmed.ncbi.nlm.nih.gov/29097735/

Cardiac Mitochondrial Nitric Oxide: A Regulator of Heart Rate? American Journal of Hypertension, Volume 21, Issue 4, April 2008, Pages 377–381. https://academic.oup.com/ajh/article/21/4/377/152122

Neuronal nitric oxide facilitates vagal chronotropic and dromotropic actions on the heart. J Auton Nerv Syst. 1999 Feb 15;75(2-3):136-46. https://pubmed.ncbi.nlm.nih.gov/10189115/

Exercise, micronutrients and the heart

Repeated mild exposure to low stress results in increased resistance of cells and organisms to subsequent stress exposure through biochemical adaptations that improve stress resistance. This applies to exercise, environmental and mental stress and supplements that work by inducing stress. On a cellular level, all types of stress cause similar effects.

Overpower contains botanicals that are categorized as ‘adaptogens’ – stress-response modifying compounds that increase an organism’s resistance to stress by increasing its ability to adapt. A characteristic feature of adaptogens is that they act as ‘eustressors’, or good stressors, and as mild stress (or exercise) mimetics that induce stress-protective responses.

The heart displays remarkable adaptability during acute and long-term bouts of physical exertion – the heart can increase its pumping capacity by 4-8 times as measured by cardiac output, which is driven by a 3-4 fold increase in heart rate.

Exercise stress helps your heart muscle become more efficient in pumping blood throughout your body – the heart pushes out more blood with each beat, allowing it to beat slower. With regular exercise, the blood flow in the small blood vessels around your heart improves and the heart tissue does a better job of pulling oxygen from blood.

Multiple micronutrients and their oral supplementation have been shown to have an influence on heart function – blood pressure, blood flow, heart rhythm, heart rate or heart rate recovery. These include compounds such as calcium, potassium, folate, ubiquinone and diverse antioxidants and plant based compounds.

Overpower contains five compounds with varying levels of scientific evidence to back their effects on heart rate. We’ll take a look at  each of them below. As the purpose of Overpower is to enhance performance – and as the heart rate is one of the fastest physiological parameters to react to an increase in physical load, we’ve paid special attention to formulate a product that maintains a lower heart rate vs. the baseline. 

Exercise clearly offers the most substantiated benefits for overall health, but timely supplementation with exercise mimetics can offer an effective adjunct to athletic activity. The complexity of heart function and control show that it might not ever be possible to mimic all of the complex molecular, physiological and health effects of exercise with other means. 

It however takes significant training time to change heart rate variables and precise supplementation can augment and speed up the process. The resting heart rate-decreasing effect takes on average, three months with three training sessions per week to start. Triggering molecular events engaged by exercise through supplementation can also be utilized as a performance- enhancing method independent of exercise.

References

Exercise and Cardiovascular Health, Circulation, 7 Jan. 2003. https://www.ahajournals.org/doi/full/10.1161/01.CIR.0000048890.59383.8D

Molecular Mechanisms Underlying Cardiac Adaptation to Exercise. Cell Metab. 2017 May 2; 25(5): 1012–1026. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512429/

Effects of Exercise on the Resting Heart Rate: A Systematic Review and Meta-Analysis of Interventional Studies. J Clin Med. 2018 Dec; 7(12): 503. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306777/

Trained men display increased basal heat shock protein content of skeletal muscle. Med Sci Sports Exerc. 2008 Jul;40(7):1255-62. https://pubmed.ncbi.nlm.nih.gov/18580405/

Physiological adaptations to interval training and the role of exercise intensity. Journal of Physiology, 17 Oct. 2016. https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP273196

Exercise improves mitochondrial and redox-regulated stress responses in the elderly: better late than never! Biogerontology. 2015 Apr;16(2):249-64.https://pubmed.ncbi.nlm.nih.gov/25537184/

Acute exercise stress promotes Ref1/Nrf2 signalling and increases mitochondrial antioxidant activity in skeletal muscle. Exp Physiol. 2016 Mar;101(3):410-20. https://pubmed.ncbi.nlm.nih.gov/26682532/

AMPK and PPARdelta agonists are exercise mimetics. Cell, Aug. 8, 2008. https://pubmed.ncbi.nlm.nih.gov/18674809/

Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals. Annals of the New York Academy of Sciences, 2017. https://www.semanticscholar.org/paper/Understanding-adaptogenic-activity%3A-specificity-of-Panossian/bda950298c31fbbdce47976ad2311f02c819eb97

Cordyceps spp.

One of the most profound functions of Cordyceps is its ability to stabilise heart beat and correct heart arrhythmia. The research has shown that administration of Cordyceps can lower high blood pressure, correct cardiac arrhythmia and reduce the duration of cardiac arrhythmia.

Cordyceps is officially approved in China for the treatment of arrhythmia, a condition in which the heartbeat is too slow, too fast or irregular.

The mechanism of action is thought to be the adenosine contents of Cordyceps and the activation of adenosine receptors. Adenosine is a purine nucleoside, most commonly recognized with the molecule adenosine triphosphate, or ATP. Adenosine plays a critical role in regulating cardiac function, including heart rate, contractility, and coronary flow.

In the context of exercise performance, a human study done with ‘Peak 02’ mushroom blend by Compounds Solutions, with Cordyceps as its main ingredient, recorded improvements in exercise heart rates at 21 days of Cordyceps consumption. However, there were differences in strength of the effect between participants of different fitness levels.

References

Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. Chapter 5: Cordyceps as an Herbal Drug. https://www.ncbi.nlm.nih.gov/books/NBK92758/

Adenosine Receptors and the Heart: Role in Regulation of Coronary Blood Flow and Cardiac Electrophysiology. Handb Exp Pharmacol. 2009; (193): 161–188. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913612/

Cardiovascular protection and antioxidant activity of the extracts from the mycelia of Cordyceps sinensis act partially via adenosine receptors. Phytother Res. 2013 Nov;27(11):1597-604. https://pubmed.ncbi.nlm.nih.gov/23192916/

Endogenous adenosine is an antiarrhythmic agent. Circulation. 1995 Mar 15;91(6):1761-7. https://pubmed.ncbi.nlm.nih.gov/7882485/

The Effects of High and Low-Dose Cordyceps Militaris-Containing Mushroom Blend Supplementation After Seven and Twenty-Eight Days. American Journal of Sports Science 2018; 6(1): 1-7. https://www.researchgate.net/publication/330284732_The_Effects_of_High_and_Low-Dose_Cordyceps_Militaris-Containing_Mushroom_Blend_Supplementation_After_Seven_and_Twenty-Eight_Days

Mucuna pruriens

L-DOPA, a constituent of Mucuna pruriens and a neurotransmitter precursor, has been shown to reduce excessive sympathetic nervous system activity with subsequent reduction in heart rate resulting from modulation of vagus nerve activity.

The vagus nerve is the longest and most complex of the 12 pairs of cranial nerves that emanate from the brain. It transmits information to or from the surface of the brain to tissues and organs elsewhere in the body. The vagus nerve is responsible for such varied tasks as decreasing the heart rate, sweating, muscle movements in the mouth, including speech and keeping the larynx open for breathing.

Independent of its L-DOPA contents, Mucuna Pruriens extract has been shown to have direct  protective action on the heart function in an animal model. The mechanism is thought to include direct action on the heart’s upper chamber, but the exact MoA is unknown.

References

Effect of l-dopa on sympathetic nerve activity and blood pressure in the spontaneously hypertensive rat. Circulation Research. 1978;43:24–28. https://www.ahajournals.org/doi/abs/10.1161/01.res.43.1.24

The effect of heart rate on the heart rate variability response to autonomic interventions. Front Physiol. 2013 Aug 26;4:222. https://pubmed.ncbi.nlm.nih.gov/23986716/

Effect of Mucuna pruriens Seed Extract Pretreatment on the Responses of Spontaneously Beating Rat Atria and Aortic Ring to Naja sputatrix (Javan Spitting Cobra) Venom. Evid Based Complement Alternat Med. 2012; 2012: 486390. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3137961/

Shilajit

Shilajit is reported to increase the oxygen-carrying capacity of the blood, improve circulation, augment oxygen levels in active tissues and maintain adequate oxygen levels during a low-oxygen state. These effects offer a plausible reasoning for the generic cardioprotective effects it displays.

In an animal model study, Shilajit was found to reduce the heart rate in a dose-dependent manner while the doses were in the normal supplemental range. The authors speculate that ‘the probable reason for this positive chronotropic effect may be due to mimicking of adrenaline- and noradrenaline-like effect or a change in calcium ion levels’. In the heart, calcium ion is crucial for the regulation of heart contraction and intracellular signaling.

References

The effects of Shilajit supplementation on fatigue-induced decreases in muscular strength and serum hydroxyproline levels. Journal of the International Society of Sports Nutrition volume 16, Article number: 3 (2019). https://jissn.biomedcentral.com/articles/10.1186/s12970-019-0270-2

Parasympathomimetic effect of shilajit accounts for relaxation of rat corpus cavernosum. Am J Mens Health. 2013 Mar;7(2):119-27. https://pubmed.ncbi.nlm.nih.gov/23060465/

Cardioprotective Effect of Mumie (Shilajit) on Experimentally Induced Myocardial Injury. Cardiovascular Toxicology volume 14, pages 214–221(2014). https://link.springer.com/article/10.1007/s12012-014-9245-3

Effect of shilajit on the heart of Daphnia: A preliminary study. J Ayurveda Integr Med. 2012 Jan;3(1):3-5. https://pubmed.ncbi.nlm.nih.gov/22529672/

Rhodiola rosea

Rhodiola rosea has been shown to exert multiple effects on heart function. The presumed mechanism of action of these cardiovascular effects is increased nitric oxide synthesis through the activation of the energy-sensing AMPK enzyme, which results in modulation of oxidative stress in the heart. In an animal model, Rhodiola rosea has been shown to maintain healthy nitric oxide levels and reduce oxidative stress in the heart while under low oxygen conditions.

AMPK is activated in a low ATP (energy depleted) state. The net effect of AMPK activation is to halt energy consuming pathways and promote energy conserving cellular pathways. In the heart, AMPK activation lowers the heart rate and appears to regulate the energy status of the heart cells, and maintain the heart muscle and its electrical pacemaker in optimal condition.

Another mechanism of cardiovascular action by Rhodiola is the activation of neuropeptide Y and Heat Shock Proteins. Neuropeptide Y is a stress–responsive hormone widely distributed in the central and peripheral nervous system, which acts as an anxiolytic and inhibits sympathetic activity, which results in lowering blood pressure and heart rate. Heat shock proteins are a family of proteins that are produced by cells in response to exposure to stressful conditions.

In the context of human performance, a human study recorded substantial decreases in heart rates (vs. a placebo) and noted a significant reduction in the average heart rate during the Rhodiola rosea treatment, and stated that ‘....this is very likely a substantial effect’. This result has been replicated in another study, which found that Rhodiola rosea ingestion significantly lowered heart rates at 6 minutes’ time during an incremental bicycle test to exhaustion. A double-blind, placebo-controlled study on humans found that Rhodiola enabled higher sustained workloads at 170 BPM, and improved post-exercise heart rate recovery. 

References

A double-blind, placebo-controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR-5 extract on the fatigue of students caused by stress during an examination period with a repeated low-dose regimen. Phytomedicine. 2000 Apr;7(2):85-9. https://pubmed.ncbi.nlm.nih.gov/10839209/

The effects of an acute dose of Rhodiola rosea on endurance exercise performance. J Strength Cond Res. 2013 Mar;27(3):839-47. https://pubmed.ncbi.nlm.nih.gov/23443221/

Acute Rhodiola rosea intake can improve endurance exercise performance. Int J Sport Nutr Exerc Metab. 2004 Jun;14(3):298-307. https://pubmed.ncbi.nlm.nih.gov/15256690/

Adaptogens stimulate neuropeptide Y and Hsp72 expression and release in neuroglia cells. Front. Neurosci., 01 February 2012. https://www.frontiersin.org/articles/10.3389/fnins.2012.00006/full

The protection of salidroside of the heart against acute exhaustive injury and molecular mechanism in rat. Oxid Med Cell Longev. 2013;2013:507832. https://pubmed.ncbi.nlm.nih.gov/24454984/

Oxidative stress improves coronary endothelial function through activation of the pro-survival kinase AMPK. Aging (Albany NY). 2013 Jul;5(7):515-30. https://pubmed.ncbi.nlm.nih.gov/24018842/

Panax Ginseng

Ginseng supplementation has been shown to have significant effect on the heart parameters such as heart rate and blood pressure during exercise and at rest, both in trained and untrained humans. Ginseng helps increase maximal heart rate and blood pressure during exercise and increases the cardiac output and blood circulation and therefore oxygen delivery to active muscles.

Similar to Rhodiola rosea’s cardiovascular mechanism of action, Ginseng increased nitric oxide synthesis through the activation of the energy sensing AMPK enzyme, which results in modulation of oxidative stress in the heart. Additionally, Ginseng compounds regulate antioxidant proteins which protect against oxidative damage triggered by injury and inflammation.

References

The effect of ginseng supplement on heart rate, systolic and diastolic blood pressure to resistance training in trained males. Artery Research Volume 15, September 2016, Pages 6-11. https://www.sciencedirect.com/science/article/pii/S1872931216300187

Cardiovascular Diseases and Panax ginseng: A Review on Molecular Mechanisms and Medical Applications. J Ginseng Res. 2012 Jan; 36(1): 16–26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659571/

Effect of Korean red ginseng on blood pressure and nitric oxide production. Acta Pharmacol Sin. 2000 Dec;21(12):1095-100. https://pubmed.ncbi.nlm.nih.gov/11603282/

Ginsenoside compound-Mc1 attenuates oxidative stress and apoptosis in cardiomyocytes through an AMP-activated protein kinase–dependent mechanism. J Ginseng Res. 2020 Jul; 44(4): 664–671. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322759/

Ginsenoside Rg1 Protects Cardiomyocytes Against Hypoxia/Reoxygenation Injury via Activation of Nrf2/HO-1 Signaling and Inhibition of JNK.  Cell Physiol Biochem. 2017;44(1):21-37. https://pubmed.ncbi.nlm.nih.gov/29130959/