A Healthy Heart for a Sharp Brain: Why Circulation Is Key to Mental Clarity
We often separate the heart and brain in medicine — one treated by cardiologists, the other by neurologists. But in reality, they are intimately connected. Your brain is only as healthy as its blood supply, and that blood supply is heavily dependent on your cardiovascular system [ref1].
When your circulation becomes constricted, your brain is the first to suffer — and the short-term negative effects can include brain fog, poor concentration, memory loss, anxiety, and fatigue. If the condition becomes chronic, you may develop Alzheimer's, Parkinson's, or other neurodegenerative diseases [ref2].
Circulation Is Life: 80% of Your Cells Are Blood Cells
Your body contains about 30 trillion human cells—and astonishingly, over 80% of them are red blood cells (erythrocytes). These cells are responsible for carrying a) oxygen and nutrients to cells, b) carbon dioxide and waste away from tissues, and c) hormones, heat, and immune cells across the body [ref3].
“More than 80% of all cells in the human body are red blood cells.”
— Sender et al., PLoS Biology, 2016 [ref4]
Your circulatory system is nothing short of extraordinary. If you were to stretch out every blood vessel in your body — arteries, veins, and microscopic capillaries — they would extend over 100,000 kilometers (about 60,000 miles). That’s enough to circle the Earth two and a half times. This immense network is tasked with one essential mission: to reach and nourish every single one of your cells.
Just as no city can function without its roads and delivery systems, no organ can function without steady, oxygen-rich blood flow. Your brain, which makes up only ~2% of your body weight, consumes ~20% of your oxygen and glucose supply. Without continuous blood flow, brain cells begin to die within minutes [ref5].
This makes the heart and circulation system a true support system for the brain — not the other way around.
CO₂: The Brain’s Master Regulator of Blood Flow
We often think of oxygen as the most important gas for brain function. But in reality, carbon dioxide (CO₂) is the primary regulator of cerebral blood flow. Your brain’s blood vessels are exquisitely sensitive to even small changes in CO₂.
When CO₂ levels rise, brain vessels dilate, increasing blood flow and delivering more oxygen. When CO₂ levels drop, from overbreathing or inactivity, those same vessels constrict — reducing brain perfusion and impairing oxygen delivery, even when oxygen levels are normal. This makes CO₂ not just a passive waste gas, but a key homeostatic signal for brain oxygenation.
“CO₂ is the most potent physiological regulator of cerebral blood flow.”
— Willie CK et al., Journal of Physiology, 2014 [ref6]
“For every 1 mmHg drop in arterial CO₂ (PaCO₂), cerebral blood flow decreases by 2–4%.”
— Ainslie PN & Duffin J, Journal of Physiology, 2009 [ref7]
The Bohr Effect in Action
Ironically, when we breathe too much in an attempt to “oxygenate our body better,” we actually reduce CO₂ levels — and this constricts cerebral blood vessels, reducing oxygen delivery to brain cells. This phenomenon, known as the Bohr effect, shows that oxygen release from hemoglobin depends on CO₂ being present.
“Low CO₂ makes hemoglobin hold onto oxygen more tightly, which can impair delivery to tissues — especially in the brain.”
— Bohr et al., 1904; confirmed in modern physiology textbooks [ref8]
Why This Matters for Mental Clarity
When CO₂ levels drop, cerebral blood flow decreases, brain oxygenation declines, and symptoms like brain fog, lightheadedness, anxiety, and reduced cognitive performance begin to appear.
This explains why chronic overbreathing, even at a subtle level, may play a hidden role in:
- POTS and orthostatic intolerance
- Migraines and tension headaches
- Alzheimer’s and Parkinson’s
- Depression, anxiety, and panic disorders
- ADHD, mental sluggishness, and fatigue
The solution? Support your brain with every breath. Breathe through your nose, keep your breathing low, slow, and small. Add in regular, low-intensity movement like Breath Walking to activate your natural circulation pumps and preserve your inner calm.
Title: Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders
Authors: Zlokovic BV.
Journal: Nat Rev Neurosci. 2011 Nov 3;12(12):723-38. doi: 10.1038/nrn3114. PMID: 22048062; PMCID: PMC4036520.
Link to full text: Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders 
Abstract: The neurovascular unit (NVU) comprises brain endothelial cells, pericytes or vascular smooth muscle cells, glia and neurons. The NVU controls blood–brain barrier (BBB) permeability and cerebral blood flow, and maintains the chemical composition of the neuronal ‘milieu’, which is required for proper functioning of neuronal circuits. Recent evidence indicates that BBB dysfunction is associated with the accumulation of several vasculotoxic and neurotoxic molecules within brain parenchyma, a reduction in cerebral blood flow, and hypoxia. Together, these vascular-derived insults might initiate and/or contribute to neuronal degeneration. This article examines mechanisms of BBB dysfunction in neurodegenerative disorders, notably Alzheimer’s disease, and highlights therapeutic opportunities relating to these neurovascular deficits.
Title: Alzheimer's disease is a vasocognopathy: a new term to describe its nature
Authors: de la Torre JC.
Journal: Neurol Res. 2004 Jul;26(5):517-24. doi: 10.1179/016164104225016254. PMID: 15265269.
Link to PubMed: Alzheimer's disease is a vasocognopathy: a new term to describe its nature 
Abstract: Considerable evidence now indicates that Alzheimer's disease (AD) is a vascular disorder with neurodegenerative consequences. As a result, AD and vascular dementia (VaD) can each be described as a 'vasocognopathy'. The term better describes the origin of the disease (vaso: vessel/blood flow), its primary effect on a system (-cogno: relating to cognition) and its clinical course (-pathy: disorder). Evidence that AD is a vasocognopathy is partly supported by the following multidisciplinary findings: (1) epidemiologic studies linking AD and vascular risk factors to cerebral hypoperfusion; (2) evidence that AD and vascular dementia (VaD) share practically all reported risk factors; (3) evidence that pharmacotherapy which increases or improves cerebral perfusion lowers AD symptoms; (4) evidence of preclinical detection of AD candidates using regional cerebral perfusion and glucose uptake studies; (5) evidence of overlapping clinical symptoms in AD and VaD; (6) evidence of parallel cerebrovascular and neurodegenerative pathologic markers (including plaques and tangles) in AD and VaD; (7) evidence that cerebral infarction increases AD incidence by 50%; (8) evidence that chronic brain hypoperfusion can trigger hypometabolic, cognitive and neurodegenerative changes typical of AD; (9) evidence that most autopsied AD brains contain cerebrovascular pathology; (10) evidence that mild cognitive impairment (a transition stage for AD) converts to AD or VaD in 48% and 56% of cases, respectively, within several years. The collective evidence presented here poses a powerful argument for the re-classification of AD as a vascular disorder. Re-classification would allow a new strategy that could result in the tactical development and application of genuinely effective treatments, provide earlier diagnosis and reduce AD prevalence by focusing on the root of the problem.
Title: The microcirculation as a functional system
Authors: Ellis CG, Jagger J, Sharpe M.
Journal: Crit Care. 2005;9 Suppl 4(Suppl 4):S3-8. doi: 10.1186/cc3751. Epub 2005 Aug 25. PMID: 16168072; PMCID: PMC3226163.
Link to full text: The microcirculation as a functional system
Abstract: This review examines experimental evidence that the microvascular dysfunction that occurs early in sepsis is the critical first stage in tissue hypoxia and organ failure. A functional microvasculature maintains tissue oxygenation despite limitations on oxygen delivery from blood to tissue imposed by diffusion; the density of perfused (functional) capillaries is high enough to ensure appropriate diffusion distances, and arterioles regulate the distribution of oxygen within the organ precisely to where it is needed. Key components of this regulatory system are the endothelium, which communicates and integrates signals along the microvascular network, and the erythrocytes, which directly monitor and regulate oxygen delivery. During hypovolemic shock, a functional microvasculature responds to diminish the impact of a decrease in oxygen supply on tissue perfusion. However, within hours of the onset of sepsis, a dysfunctional microcirculation is, due to a loss of functional capillary density and impaired regulation of oxygen delivery, unable to maintain capillary oxygen saturation levels and prevent the rapid onset of tissue hypoxia despite adequate oxygen supply to the organ. The mechanism(s) responsible for this dysfunctional microvasculature must be understood in order to develop appropriate management strategies for sepsis.
Title: Revised Estimates for the Number of Human and Bacteria Cells in the Body
Authors: Sender R, Fuchs S, Milo R.
Journal: PLoS Biol. 2016 Aug 19;14(8):e1002533. doi: 10.1371/journal.pbio.1002533. PMID: 27541692; PMCID: PMC4991899.
Link to full text: Revised Estimates for the Number of Human and Bacteria Cells in the Body
Abstract: Reported values in the literature on the number of cells in the body differ by orders of magnitude and are very seldom supported by any measurements or calculations. Here, we integrate the most up-to-date information on the number of human and bacterial cells in the body. We estimate the total number of bacteria in the 70 kg "reference man" to be 3.8·1013. For human cells, we identify the dominant role of the hematopoietic lineage to the total count (≈90%) and revise past estimates to 3.0·1013 human cells. Our analysis also updates the widely-cited 10:1 ratio, showing that the number of bacteria in the body is actually of the same order as the number of human cells, and their total mass is about 0.2 kg.
Title: Demonstration of impaired neurovascular coupling responses in TG2576 mouse model of Alzheimer's disease using functional laser speckle contrast imaging
Authors: Tarantini S, Fulop GA, Kiss T, Farkas E, Zölei-Szénási D, Galvan V, Toth P, Csiszar A, Ungvari Z, Yabluchanskiy A.
Journal: Geroscience. 2017 Aug;39(4):465-473. doi: 10.1007/s11357-017-9980-z. Epub 2017 Jun 3. PMID: 28578467; PMCID: PMC5636768.
Link to full text: Demonstration of impaired neurovascular coupling responses in TG2576 mouse model of Alzheimer's disease using functional laser speckle contrast imaging
Abstract: Increasing evidence from epidemiological, clinical, and experimental studies indicates that cerebromicrovascular dysfunction and microcirculatory damage play critical roles in the pathogenesis of many types of dementia in the elderly, including both vascular cognitive impairment (VCI) and Alzheimer's disease. Vascular contributions to cognitive impairment and dementia (VCID) include impairment of neurovascular coupling responses/functional hyperemia ("neurovascular uncoupling"). Due to the growing interest in understanding and pharmacologically targeting pathophysiological mechanisms of VCID, there is an increasing need for sensitive, easy-to-establish methods to assess neurovascular coupling responses. Laser speckle contrast imaging (LSCI) is a technique that allows rapid and minimally invasive visualization of changes in regional cerebromicrovascular blood perfusion. This type of imaging technique combines high resolution and speed to provide great spatiotemporal accuracy to measure moment-to-moment changes in cerebral blood flow induced by neuronal activation. Here, we provide detailed protocols for the successful measurement in neurovascular coupling responses in anesthetized mice equipped with a thinned-skull cranial window using LSCI. This method can be used to evaluate the effects of anti-aging or anti-AD treatments on cerebromicrovascular health.
Title: Integrative regulation of human brain blood flow
Authors: Willie CK, Tzeng YC, Fisher JA, Ainslie PN.
Journal: J Physiol. 2014 Mar 1;592(5):841-59. doi: 10.1113/jphysiol.2013.268953. Epub 2014 Jan 6. PMID: 24396059; PMCID: PMC3948549.
Link to full text: Integrative regulation of human brain blood flow
Abstract: Herein, we review mechanisms regulating cerebral blood flow (CBF), with specific focus on humans. We revisit important concepts from the older literature and describe the interaction of various mechanisms of cerebrovascular control. We amalgamate this broad scope of information into a brief review, rather than detailing any one mechanism or area of research. The relationship between regulatory mechanisms is emphasized, but the following three broad categories of control are explicated: (1) the effect of blood gases and neuronal metabolism on CBF; (2) buffering of CBF with changes in blood pressure, termed cerebral autoregulation; and (3) the role of the autonomic nervous system in CBF regulation. With respect to these control mechanisms, we provide evidence against several canonized paradigms of CBF control. Specifically, we corroborate the following four key theses: (1) that cerebral autoregulation does not maintain constant perfusion through a mean arterial pressure range of 60-150 mmHg; (2) that there is important stimulatory synergism and regulatory interdependence of arterial blood gases and blood pressure on CBF regulation; (3) that cerebral autoregulation and cerebrovascular sensitivity to changes in arterial blood gases are not modulated solely at the pial arterioles; and (4) that neurogenic control of the cerebral vasculature is an important player in autoregulatory function and, crucially, acts to buffer surges in perfusion pressure. Finally, we summarize the state of our knowledge with respect to these areas, outline important gaps in the literature and suggest avenues for future research.
Title: Integration of cerebrovascular CO2 reactivity and chemoreflex control of breathing: mechanisms of regulation, measurement, and interpretation
Authors: Ainslie PN, Duffin J.
Journal: Am J Physiol Regul Integr Comp Physiol. 2009 May;296(5):R1473-95. doi: 10.1152/ajpregu.91008.2008. Epub 2009 Feb 11. PMID: 19211719.
Link to full text: Integration of cerebrovascular CO2 reactivity and chemoreflex control of breathing: mechanisms of regulation, measurement, and interpretation
Abstract: Cerebral blood flow (CBF) and its distribution are highly sensitive to changes in the partial pressure of arterial CO(2) (Pa(CO(2))). This physiological response, termed cerebrovascular CO(2) reactivity, is a vital homeostatic function that helps regulate and maintain central pH and, therefore, affects the respiratory central chemoreceptor stimulus. CBF increases with hypercapnia to wash out CO(2) from brain tissue, thereby attenuating the rise in central Pco(2), whereas hypocapnia causes cerebral vasoconstriction, which reduces CBF and attenuates the fall of brain tissue Pco(2). Cerebrovascular reactivity and ventilatory response to Pa(CO(2)) are therefore tightly linked, so that the regulation of CBF has an important role in stabilizing breathing during fluctuating levels of chemical stimuli. Indeed, recent reports indicate that cerebrovascular responsiveness to CO(2), primarily via its effects at the level of the central chemoreceptors, is an important determinant of eupneic and hypercapnic ventilatory responsiveness in otherwise healthy humans during wakefulness, sleep, and exercise and at high altitude. In particular, reductions in cerebrovascular responsiveness to CO(2) that provoke an increase in the gain of the chemoreflex control of breathing may underpin breathing instability during central sleep apnea in patients with congestive heart failure and on ascent to high altitude. In this review, we summarize the major factors that regulate CBF to emphasize the integrated mechanisms, in addition to Pa(CO(2)), that control CBF. We discuss in detail the assessment and interpretation of cerebrovascular reactivity to CO(2). Next, we provide a detailed update on the integration of the role of cerebrovascular CO(2) reactivity and CBF in regulation of chemoreflex control of breathing in health and disease. Finally, we describe the use of a newly developed steady-state modeling approach to examine the effects of changes in CBF on the chemoreflex control of breathing and suggest avenues for future research.
Title: Concerning a Biologically Important Relationship - The Influence of the Carbon Dioxide Content of Blood on its Oxygen Binding
Authors: Bohr, C., Hasselbalch, K., & Krogh, A.
Journal: Skandinavisches Archiv Für Physiologie 16.2 (1904): 402-412.
Link to full text: Concerning a Biologically Important Relationship - The Influence of the Carbon Dioxide Content of Blood on its Oxygen Binding
Abstract: Complexes of hemoglobin and carbon dioxide have been known for a long time; however, so far all researchers have regarded the oxygen uptake of the blood and its carbon dioxide uptake as two independent processes. Bohr found instead in the cited discussion that even though the carbon dioxide-uptake in the presence of oxygen remains uninfluenced, the oxygen uptake of the blood is usually reduced if a certain amount of carbon dioxide is present. However, from a quantitative point of view, the results were only reproducible with a relatively large error which may be due to great variability of the hemoglobin molecule.
