Nasal Airflow Activates Broad Regions of the Olfactory Bulb

Key Points

• Nasal breathing information is “encoded” by olfactory sensory neurons in the olfactory bulb

• Breathing activates broad regions of the olfactory bulb, with the intensity changing as total breathing volume changes

• The neural activity stimulated by nasal breathing helps explain how breathing can have immediate physiological effects throughout the body

The Breathing Diabetic Summary

The olfactory bulb (OB) and its neurons (olfactory sensory neurons, OSNs) can sense both odors and airflow.  However, previous studies have rarely examined how airflow is actually encoded by the OB and OSNs.  This study used fMRI and local field potential to figure out how airflow activity is mapped in the OB. 

They studied mice under different airflow stimulation (these can be thought of as different breathing patterns because the mechanical stimulation was occurring through their noses).  The different breathing paradigms included changing respiratory rate, changing tidal volume, or changing both rate and tidal volume while keeping the total airflow the same (that is, keeping Rate X Volume = Constant). 

The results showed that airflow stimulation activated broad regions of the OB.  Odor stimulation, on the other hand, had more localized activity maps.  Furthermore, the overall structure of the activity maps was similar regardless of which breathing paradigm was being studied.  Only the intensity of the signal changed with total airflow.  Greater total volume led to more intense activity in the OB. 

Another interesting result was that nasal airflow affected the physiological state of the mice.  Their resting heart and breathing rates slowed, and EEG power declined in specific ranges. 

These results are important because they show for the first time that nasal breathing information is encoded in the olfactory bulb.  We know that breathing can directly influence emotional state, for example, providing a calming effect.  And, there have been several studies showing a direct correlation between breathing, brain activity, memory, and behavior.  Here, we see why.   

Nasal breathing information is imprinted in the OB.  The OB then projects onto the limbic system, which regulates emotions, olfaction, and the autonomic nervous system.  This helps explain the wide-ranging benefits of slow breathing and how breathing can have such immediate effects on our physiological state.

To summarize, this is the first study to show that nasal airflow elicits broad activity maps in the olfactory bulb.  The patterns are robust and change only in intensity when total airflow is altered.  The effects of nasal respiration on the olfactory bulb are then projected on the limbic system, helping explain how breathing can quickly impact physiological state.

Abstract

Olfactory sensory neurons (OSNs) can sense both odorants and airflows. In the olfactory bulb (OB), the coding of odor information has been well studied, but the coding of mechanical stimulation is rarely investigated. Unlike odor-sensing functions of OSNs, the airflow-sensing functions of OSNs are also largely unknown. Here, the activity patterns elicited by mechanical airflow in male rat OBs were mapped using fMRI and correlated with local field potential recordings. In an attempt to reveal possible functions of airflow sensing, the relationship between airflow patterns and physiological parameters was also examined. We found the following: (1) the activity pattern in the OB evoked by airflow in the nasal cavity was more broadly distributed than patterns evoked by odors; (2) the pattern intensity increases with total airflow, while the pattern topography with total airflow remains almost unchanged; and (3) the heart rate, spontaneous respiratory rate, and electroencephalograph power in the β band decreased with regular mechanical airflow in the nasal cavity. The mapping results provide evidence that the signals elicited by mechanical airflow in OSNs are transmitted to the OB, and that the OB has the potential to code and process mechanical information. Our functional data indicate that airflow rhythm in the olfactory system can regulate the physiological and brain states, providing an explanation for the effects of breath control in meditation, yoga, and Taoism practices.

SIGNIFICANCE STATEMENT Presentation of odor information in the olfactory bulb has been well studied, but studies about breathing features are rare. Here, using blood oxygen level-dependent functional MRI for the first time in such an investigation, we explored the global activity patterns in the rat olfactory bulb elicited by airflow in the nasal cavity. We found that the activity pattern elicited by airflow is broadly distributed, with increasing pattern intensity and similar topography under increasing total airflow. Further, heart rate, spontaneous respiratory rate in the lung, and electroencephalograph power in the β band decreased with regular airflow in the nasal cavity. Our study provides further understanding of the airflow map in the olfactory bulb in vivo, and evidence for the possible mechanosensitivity functions of olfactory sensory neurons.

Journal Reference:

Wu R, Liu Y, Wang L, Li B, Xu F.  Activity patterns elicited by airflow in the olfactory bulb and their possible functions.  J Neurosci. 2017;37(44):10700-10711. doi: 10.1523/JNEUROSCI.2210-17.2017.

Diaphragmatic breathing improves subjective and physiological indicators of anxiety

Key Points

• Diaphragmatic breathing reduces anxiety as measured on the Beck Anxiety Inventory

• Diaphragmatic breathing reduces physiological indicators of anxiety, including breathing rate, heart rate, and skin conductance

The Breathing Diabetic Summary

We’ve all been told to just “take a deep breath.”  As I’ve argued before, that’s not always the best advice.  However, it might not be the worst advice either.

We know that controlling your breath improves autonomic balance and improves several markers of cardiovascular function.  This paper wanted to examine the effects of diaphragmatic breathing on both subjective and physiological indicators of anxiety.

To do this, they studied 30 patients with mild-to-moderate anxiety.  The participants were broken up into a control (n=15) group and diaphragmatic breathing relaxation (DBR; n=15) group.

The DBR group was given instruction on diaphragmatic breathing over an 8-week period.  They also were instructed to practice DBR twice daily, completing 10 breaths with each practice.

(Here is my only qualm with this paper. They did not describe exactly what the DBR technique was.  They just said that the patients received DBR training and were instructed to practice at home and during training sessions with the investigators.  Therefore, we cannot replicate their DBR exercise for ourselves.)

After the 8-week program, the participants in the DBR group significantly reduced their anxiety on the Beck Anxiety Inventory (BAI), a standardized questionnaire used to assess anxiety.  Their average scores dropped from ~19 down to ~5 (lower is better).

Moreover, physiological indicators of anxiety also reduced in the DBR group.  For example, heart rate, breathing rate, and skin conductivity all decreased, indicating reductions in anxiety.

Overall, these results indicate that diaphragmatic breathing improves anxiety from both subjective and physiological perspectives.  That is, it works.  Thus, we can use deep breathing anytime we (or our clients or friends) feel overwhelmed and know that we are changing our physiology to promote a more relaxed state.

Abstract from Paper

PURPOSE: To evaluate the effectiveness on reducing anxiety of a diaphragmatic breathing relaxation (DBR) training program.

DESIGN AND METHODS: This experimental, pre-test-post-test randomized controlled trial with repeated measures collected data using the Beck Anxiety Inventory and biofeedback tests for skin conductivity, peripheral blood flow, heart rate, and breathing rate.

FINDINGS: The experimental group achieved significant reductions in Beck Anxiety Inventory scores (p < .05), peripheral temperature (p = .026), heart rate (p = .005), and breathing rate (p = .004) over the 8-week training period. The experimental group further achieved a significant reduction in breathing rate (p < .001).

PRACTICE IMPLICATIONS: The findings provide guidance for providing quality care that effectively reduces the anxiety level of care recipients in clinical and community settings.

Journal Reference:

Chen YF, Huang XY, Chien CH, Cheng JF. The effectiveness of diaphragmatic breathing relaxation training for reducing anxiety. Perspect Psychiatr Care. 2017;53(4):329-336.

Intermittent hypoxia increases brain blood flow by 20%

Key Points

• Intermittent hypoxia (IH) increases brain blood flow, even with low CO2

• IH increases fractional oxygen extraction in the brain

• IH might be a useful before a workout, competition, or presentation to increase brain blood flow and focus

The Breathing Diabetic Summary

Your brain consumes almost 20% of your oxygen at rest.  Therefore, during intermittent hypoxia (IH), it makes sense that the body would compensate to make sure the brain gets the oxygen it needs.

However, previous studies are conflicting because when oxygen is reduced, we typically start breathing more.  This gets rid of too much carbon dioxide (CO2), leading to hypocapnia (low CO2).

CO2 is a main driver of cerebral vasodilation.  That is, it increases brain blood flow.  Thus, if CO2 is reduced, we would expect less blood flow to the brain. 

This study aimed to see how these factors played out during cyclic IH.  Would the reduced O2 increase brain blood flow, or would it be offset by reduced CO2?

They recruited 8 healthy men that were ~25 years old.  The participants inhaled O2 at 10% for 6 min to induce hypoxia.  They then breathed normal room air for 4 min.  This cycle was repeated 5 times.  Measurements were taken after the 1st and 5th bouts to see how responses changed during progressive hypoxia exposures.

During the bouts of hypoxia, blood oxygen saturation dropped to ~67%, which is below the therapeutic range of IH.  However, the authors reported that none of the subjects felt discomfort or stress.

Overall, the results revealed that brain blood flow increased by ~20%.  Increases in brain blood flow were significantly greater during the 5th vs. the 1st bout of hypoxia, suggesting a cumulative effect of hypoxia exposures.  The participants dropped CO2 by 4 mm Hg, yet their brain blood flow still increased significantly.  Thus, the increased brain blood flow from hypoxia “overpowered” the reduced blood flow from hypocapnia.

Fractional oxygen extraction in the brain also increased significantly after the 1st bout and remained elevated during the rest of the protocol.  Muscle oxygen extraction, on the other hand, dropped during the procedure, suggesting that the brain gets priority during times of hypoxia.

Statistical analysis revealed that major increases in brain blood flow occurred at about 86% SpO2.  This is something we can easily achieve using breath holds.  In fact, Principle 3 recommends hypercapnic (high CO2) breath holds.  Because both hypoxia and high CO2 cause cerebral vasodilation, we can speculate that brain blood flow would be increased even more using this protocol.

Finally, from a practical perspective, this research supports the idea of practicing breath holds before a workout, competition, or presentation. The increased brain blood flow will help focus your mind and prepare you for what’s ahead.

Abstract from Paper

Cerebral vasodilation and increased cerebral oxygen extraction help maintain cerebral oxygen uptake in the face of hypoxemia. This study examined cerebrovascular responses to intermittent hypoxemia in eight healthy men breathing 10% O2 for 5 cycles, each 6 min, interspersed with 4 min of room air breathing. Hypoxia exposures raised heart rate ( P < 0.01) without altering arterial pressure, and increased ventilation ( P < 0.01) by expanding tidal volume. Arterial oxygen saturation ([Formula: see text]) and cerebral tissue oxygenation ([Formula: see text]) fell ( P < 0.01) less appreciably in the first bout (from 97.0 ± 0.3% and 72.8 ± 1.6% to 75.5 ± 0.9% and 54.5 ± 0.9%, respectively) than the fifth bout (from 94.9 ± 0.4% and 70.8 ± 1.0% to 66.7 ± 2.3% and 49.2 ± 1.5%, respectively). Flow velocity in the middle cerebral artery ( VMCA) and cerebrovascular conductance increased in a sigmoid fashion with decreases in [Formula: see text] and [Formula: see text]. These stimulus-response curves shifted leftward and upward from the first to the fifth hypoxia bouts; thus, the centering points fell from 79.2 ± 1.4 to 74.6 ± 1.1% ( P = 0.01) and from 59.8 ± 1.0 to 56.6 ± 0.3% ( P = 0.002), and the minimum VMCA increased from 54.0 ± 0.5 to 57.2 ± 0.5 cm/s ( P = 0.0001) and from 53.9 ± 0.5 to 57.1 ± 0.3 cm/s ( P = 0.0001) for the [Formula: see text]- VMCA and [Formula: see text]- VMCA curves, respectively. Cerebral oxygen extraction increased from prehypoxia 0.22 ± 0.01 to 0.25 ± 0.02 in minute 6 of the first hypoxia bout, and remained elevated between 0.25 ± 0.01 and 0.27 ± 0.01 throughout the fifth hypoxia bout. These results demonstrate that cerebral vasodilation combined with enhanced cerebral oxygen extraction fully compensated for decreased oxygen content during acute, cyclic hypoxemia. NEW & NOTEWORTHY Five bouts of 6-min intermittent hypoxia (IH) exposures to 10% O2 progressively reduce arterial oxygen saturation ([Formula: see text]) to 67% without causing discomfort or distress. Cerebrovascular responses to hypoxemia are dynamically reset over the course of a single IH session, such that threshold and saturation for cerebral vasodilations occurred at lower [Formula: see text] and cerebral tissue oxygenation ([Formula: see text]) during the fifth vs. first hypoxia bouts. Cerebral oxygen extraction is augmented during acute hypoxemia, which compensates for decreased arterial O2 content.

Journal Reference:

Liu X, Xu D, Hall JR, et al.  Enhanced cerebral perfusion during brief exposures to cyclic intermittent hypoxemia.  J Appl Physiol.  2017;123(6):1689-1897.

Intermittent hypoxia is beneficial in sedentary, non-athletic, and clinical populations

Key Points

• Intermittent hypoxia improves cardio-autonomic function and exercise tolerance

• There are several ways to achieve intermittent hypoxia and receive benefits, including prolonged hypoxic exposure, intermittent hypoxic exposure, and intermittent hypoxic training

• Intermittent hypoxia is beneficial in sedentary and clinical populations

The Breathing Diabetic Summary

I love review papers because they summarize the key findings from the scientific literature in an easy to follow manner. Therefore, anytime I find a review study on a subject of interest, I dive right in.

This one was unique because it looked at the effects of simulated altitude on non-athletic, sedentary, and clinical populations. Most studies on simulated altitude involve elite performers, so it was interesting seeing a review paper focusing on more “everyday” people.

Using different search criteria, they identified 26 studies that have looked at intermittent hypoxia in the abovementioned populations. Within those 26 studies, they then identified 3 different methods of achieving intermittent hypoxia:

1. Prolonged hypoxic exposure (PHE): Continuous hypoxic interval, such as “live high, train low”.

2. Intermittent hypoxic exposure (IHE): Short intervals (5-10 min) of hypoxic:normoxic exposure.

3. Intermittent hypoxic training (IHT): Exercising in hypoxia.

For our purposes, IHE and IHT are the only practical methods for achieving hypoxia via breath holds. However, the results for PHE will also be included for completeness (and, maybe one day altitude tents will be affordable!).

Here, I’ll summarize the benefits they found for each method of hypoxia.

IHE:

• Reduced systemic stress

• Improved heart rate variability

• Improved autonomic balance

• Reduced blood pressure

• Greater exercise tolerance

• Longer time to exhaustion while exercising

• Hematological results were mixed. Some studies showed increased red blood cells, others didn’t.

PHE:

• Improved lung ventilation

• Improved submaximal exercise performance

• Improved blood lipid profile

• Improved blood flow to the heart

IHT:

• Increased aerobic capacity

• Increased fat burning

• Increased mitochondrial density

• Improved autonomic balance

With respect to PHE, the research suggested that at least 1 hour of 12% O2 for 2 weeks would provide the greatest benefits without side effects. They did not provide recommendations for IHE or IHT.

However, a 2014 review study showed that 3-15 episodes of 9-16% O2 is the therapeutic range for IHE. This corresponds to blood O2 saturations of approximately 82-95%.

Also, from a practical perspective, we know that we can perform walking breath holds to achieve mild IHT. Essentially, we combine the IHE protocol with walking.

Overall, this paper suggests that intermittent hypoxia has many benefits in sedentary, non-athletic, and clinical populations, including improved cardiovascular and autonomic function and increased exercise capacity.

It also showed that there are several ways to achieve those benefits: Prolonged exposure, intermittent exposure, or exposure during exercise.

I recommend that you find a modality that fits you or your client’s lifestyle that can be practiced consistently.

Abstract from Paper

BACKGROUND: The reportedly beneficial improvements in an athlete's physical performance following altitude training may have merit for individuals struggling to meet physical activity guidelines.

AIM: To review the effectiveness of simulated altitude training methodologies at improving cardiovascular health in sedentary and clinical cohorts.

METHODS: Articles were selected from Science Direct, PubMed, and Google Scholar databases using a combination of the following search terms anywhere in the article: "intermittent hypoxia," "intermittent hypoxic," "normobaric hypoxia," or "altitude," and a participant descriptor including the following: "sedentary," "untrained," or "inactive."

RESULTS: 1015 articles were returned, of which 26 studies were accepted (4 clinical cohorts, 22 studies used sedentary participants). Simulated altitude methodologies included prolonged hypoxic exposure (PHE: continuous hypoxic interval), intermittent hypoxic exposure (IHE: 5-10 minutes hypoxic:normoxic intervals), and intermittent hypoxic training (IHT: exercising in hypoxia).

CONCLUSIONS: In a clinical cohort, PHE for 3-4 hours at 2700-4200 m for 2-3 weeks may improve blood lipid profile, myocardial perfusion, and exercise capacity, while 3 weeks of IHE treatment may improve baroreflex sensitivity and heart rate variability. In the sedentary population, IHE was most likely to improve submaximal exercise tolerance, time to exhaustion, and heart rate variability. Hematological adaptations were unclear. Typically, a 4-week intervention of 1-hour-long PHE intervals 5 days a week, at a fraction of inspired oxygen (FIO2) of 0.15, was beneficial for pulmonary ventilation, submaximal exercise, and maximum oxygen consumption ([Formula: see text]O2max), but an FIO2 of 0.12 reduced hyperemic response and antioxidative capacity. While IHT may be beneficial for increased lipid metabolism in the short term, it is unlikely to confer any additional advantage over normoxic exercise over the long term. IHT may improve vascular health and autonomic balance.

Journal Reference:

Lizamore CA, Hamlin MJ.  The Use of Simulated Altitude Techniques for Beneficial Cardiovascular Health Outcomes in Nonathletic, Sedentary, and Clinical Populations: A Literature Review.  High Alt Med Biol.  2017;18(4):305-321.

Treat & reverse the root cause of diabetic complications (tissue hypoxia) with slow breathing

Key Points

• Type-1 diabetics exhibit lower resting oxygen saturation, lower cardiovascular control, reduced hypoxic chemoreflexes, and enhanced hypercapnic chemoreflexes

• The root cause of these problems is resting tissue hypoxia, which causes over-activation of the sympathetic nervous system and autonomic and cardiovascular dysfunction

• Autonomic imbalance in diabetes is largely functional, and therefore reversible

The Breathing Diabetic Summary

This is a follow-on to our previous paper on cardio-respiratory control in diabetes.  This paper, however, is a clinical study rather than a literature review.

Previous studies have shown respiratory problems in diabetics.  Previous studies also have shown cardiovascular dysfunction in diabetics.  However, no studies simultaneously examined both of these factors in an integrated fashion.  Thus, the aim of this study was to comprehensively examine cardio-respiratory function in type-1 diabetics.

The key measurements from this paper were resting oxygen saturation, baroreflex sensitivity (BRS; a marker of cardiovascular and autonomic control), and both hypoxic and hypercapnic chemoreflexes (markers of respiratory control). 

Their hypothesis: If the BRS and chemoreflexes were suppressed in diabetics, this would indicate nerve damage was present.  However, if cardiovascular function was suppressed, while chemoreflexes were enhanced, this would indicate autonomic imbalance that has a functional cause.  In this latter case, therapies aimed at restoring cardio-respiratory control (for example, slow breathing) could help prevent diabetic complications.

The study had 46 patients with type-1 diabetes and 103 age-matched control subjects.  The participants went through a variety of tests to evaluate baroreflex functioning and chemoreflexes.  For example, to measure the patients’ hypercapnic chemoreflex, oxygen was kept constant while CO2 was gradually increased.  The chemoreflex can then be measured as the slope of the relationship between minute ventilation and change in CO2 (or oxygen in the case of the hypoxic chemoreflex).  A large change in minute ventilation for a small change in CO2 would represent an enhanced hypercapnic chemoreflex.

Interestingly, the results showed that although diabetics displayed larger breathing volumes than controls, they had slightly higher CO2 levels and reduced oxygen saturation.  However, they did have an enhanced hypercapnic chemoreflex, meaning they could not tolerate changes in CO2 as well as controls.  And, somewhat surprisingly, they had a reduced hypoxic chemoreflex, meaning they could tolerate lower oxygen levels without increasing their breathing as much as controls.

The diabetics also exhibited a lower resting oxygen saturation. This is fascinating because the lower resting oxygen saturation implies a significantly reduced partial pressure of oxygen (due to the oxyhemoglobin dissociation curve). This would result in tissue hypoxia. What’s more, they cite a paper (which is now near the top of my reading list) that shows that a high HbA1c also reduces tissue oxygenation by increasing oxygen’s affinity to hemoglobin (shifting the dissociation curve to the left). 

The authors suggest that their results can be interpreted as follows: Resting tissue hypoxia, combined with a suppressed hypoxic chemoreflex, leads to an enhanced compensatory hypercapnic chemoreflex and chronic activation of the sympathetic nervous system.  This, in turn, leads to a suppression of the cardiovascular system (reduced BRS and reduced heart rate variability).  It’s a vicious cycle.

However, this is actually great news.  Their results suggest that diabetic autonomic imbalance is largely functional and not related to nerve damage.  (Remember, both the cardiovascular reflexes and the chemoreflexes would have been suppressed with nerve damage).  In fact, the authors suggest that this imbalance likely leads to nerve damage rather than being the result of it. Therefore, therapies targeting cardio-respiratory control could help reverse/prevent diabetic complications.

Finally, the authors suggest that breathing control and physical exercise could be two such therapies to restore cardio-respiratory function.  We know that slow breathing has many therapeutic benefits for the cardiovascular, autonomic, and respiratory systems.  And, we know that slow, light breathing increases CO2 and increases tissue oxygenation (due to the Bohr effect).  Now, we know that these positive benefits have the potential to stop or reverse diabetic complications. 

Abstract from Paper

BACKGROUND: Cardiovascular (baroreflex) and respiratory (chemoreflex) control mechanisms were studied separately in diabetes, but their reciprocal interaction (well known for diseases like heart failure) had never been comprehensively assessed. We hypothesized that prevalent autonomic neuropathy would depress both reflexes, whereas prevalent autonomic imbalance through sympathetic activation would depress the baroreflex but enhance the chemoreflexes.

METHODS: In 46 type-1 diabetic subjects (7.0±0.9year duration) and 103 age-matched controls we measured the baroreflex (average of 7 methods), and the chemoreflexes, (hypercapnic: ventilation/carbon dioxide slope during hyperoxic progressive hypercapnia; hypoxic: ventilation/oxygen saturation slope during normocapnic progressive hypoxia). Autonomic dysfunction was evaluated by cardiovascular reflex tests.

RESULTS: Resting oxygen saturation and baroreflex sensitivity were reduced in the diabetic group, whereas the hypercapnic chemoreflex was significantly increased in the entire diabetic group. Despite lower oxygen saturation the hypoxic chemoreflex showed a trend toward a depression in the diabetic group.

CONCLUSION: Cardio-respiratory control imbalance is a common finding in early type 1 diabetes. A reduced sensitivity to hypoxia seems a primary factor leading to reflex sympathetic activation (enhanced hypercapnic chemoreflex and baroreflex depression), hence suggesting a functional origin of cardio-respiratory control imbalance in initial diabetes.

Journal Reference:

Bianchi L, Porta C, Rinaldi A, Gazzaruso C, Fratino P, DeCata P, Protti P, Paltro R, Bernardi L. Integrated cardiovascular/respiratory control in type 1 diabetes evidences functional imbalance: Possible role of hypoxia. Int J Cardiol. 2017;244:254 – 259.

Slow breathing improves blood sugar by reducing body’s endogenous production of glucose

Key Points

• Slow breathing lowers blood sugar by reducing the liver’s production of glucose

• Slow breathing increases insulin sensitivity

• Slow breathing might be a no-cost beneficial intervention for diabetics

Breathing Blueprint Summary

This is a follow on to the previous Wilson et al. (2013) paper that described how a relaxation breathing exercise improved glycemic response in healthy college-aged humans.  In this review, the authors examine key evidence showing that breathing can potentially improve glycemic response and insulin sensitivity.  

Let’s start with some statistics. Can you believe that in 2013, ~9.3% of Americans had diabetes?!?  That’s insane.  And, pharmacy costs added up to ~$18 billion!  Breathing might not cure diabetes, but it might help reduce the costs and negative side effects of diabetics by improving our insulin sensitivity and glycemic control. Which is exactly what this paper examined.

One mechanism they found that explains why slow, relaxation breathing lowers blood sugar is reduction in sympathetic nervous system activity.  In short, the liver generates glucose via a process called gluconeogenesis.  When the sympathetic nervous system is activated, it increases this process, increasing the body’s endogenous production of glucose.  Other stress hormones, such as adrenaline, also increase the liver’s production of glucose.  By breathing slowly, we shift out of this sympathetic state, reducing the amount of glucose produced by the liver and helping reduce our blood sugar.

They also examined several studies showing that slow breathing can restore insulin sensitivity.  There were no clear mechanisms as to how slow breathing improved insulin sensitivity, but the take-home point was that it does. We will have to wait on future studies to identify exactly what’s going on “under the hood.”

Overall, this review showed scientific evidence that breathing exercises can improve glycemic control and increase insulin sensitivity.  The glucose-lowering effect of slow breathing is likely due to reduced sympathetic activity and reduced glucose production by the liver.  The improved insulin sensitivity might also be related to this, but the precise mechanism is unknown.

In any case, I think it’s safe to say that practicing Principle 1 and Principle 2 is a good idea, especially for diabetics, to improve glycemic control and insulin sensitivity.

Abstract from Paper

This is the first review of the literature on the effects of slow breathing on glycemic regulation and insulin sensitivity. While many studies have investigated the effects of yoga on individuals with diabetes, few studies have specifically focusing on the isolation of slow breathing as the principle factor in their intervention. While it is difficult to separate the exercise-related effects of yoga, there is considerable evidence that a breathing intervention is capable of increasing insulin sensitivity and improving glycemic regulation. This appears to be true both acutely and chronically in healthy individuals and those with diabetes. Yoga pranayama and the slow breathing practices that are fundamental to yoga represent a relatively low-cost and under-utilized intervention for individuals with conditions related to altered glycemic regulation and insulin sensitivity. More studies should focus on pranayama and slow breathing maneuvers to better clarify the role of respiratory modulation on glucose metabolism and insulin response.

Journal Reference:

Wilson T, Kelly KL, Baker SE. Review: Can yoga breathing exercises improve glycemic response and insulin sensitivity?. J Yoga Phys Ther. 2017;7(2). DOI: 10.4172/2157-7595.1000270.

Breathe slowly (and pause) to improve heart rate variability

Key Points

• Slow breathing at ~6 breaths/min increases heart rate variability (HRV)

• Including a post-exhalation pause enhances relaxation and makes it easier to breathe slowly

• A post-exhalation pause also enhances some HRV parameters more than continuous breathing

The Breathing Diabetic Summary

We don’t want our hearts to beat like a metronome, but to constantly be changing and adapting to the current conditions.  One way to measure this is through heart rate variability (HRV), which represents the changes in time between heartbeats.  HRV is a marker of overall health: Higher HRV is associated with better health. 

Many studies have shown that slow breathing can increase HRV.  Depending on the individual, it appears that breathing at a pace between 4 and 6 breaths/min maximizes HRV.  However, there are many ways to achieve a breathing rate of 4-6 breaths/min. 

For example, you can inhale for 5 sec, and exhale for 5 sec.  Inhale for 4 sec, exhale for 6 sec, etc.  But, these different methods might not necessarily be the best way to maximize HRV.  The current study set out to see if including a post-exhalation pause would increase HRV compared to continuous breathing with equal inhales and exhales.

Specifically, they tested two different methods for breathing at 5.5 breaths/min: 5-5 and 4-2-4.  The 5-5 protocol used a 5 sec inhale and 5 sec exhale.  The 4-2-4 protocol used a 4 sec inhale, 2 sec exhale, and 4 sec post-exhalation pause. 

Forty subjects performed the breathing protocols in a seated upright position.  They performed each breathing protocol for 6 min, followed by a 5 min rest period before starting the next one.  Along with measuring several different HRV parameters, the authors also evaluated which breathing protocol the subjects found more relaxing and easier to perform.

68% of the participants found the 4-2-4 cycle easier to follow and 63% found it more relaxing.  The authors suspect that this is a result of the shorter inhalation period, which caused less strain on the breathing muscles.  They also suspect that the post-exhalation rest period reduced the risk of hyperventilation.

There is no one single measurement for HRV.  There are high and low frequency bands, along with other parameters such as the standard deviation of the NN intervals.  In this study, they found that the 4-2-4 cycle significantly improved one aspect of HRV (high-frequency HRV), whereas the 5-5 cycle improved another (low-frequency HRV).  Thus, although the title of the paper suggests that the rest period is critical, it is important to note that both breathing protocols improved HRV in different ways.

Overall, this study shows that you can improve HRV by slowing down your breath.  Whether you adopt a post-exhalation rest or simply do slow continuous breathing is up to you. Either way, you can rest assurred you will be improving this critical indicator of overall health.

Let’s wrap up with a quote from the end of the paper that is one of my new favorites:

“With breathing interventions being relatively rapid interventions to implement and also demonstrating a wide range of positive clinical outcomes, breathing interventions warrant closer consideration from healthcare professionals.”

Abstract from Paper

Heart rate variability (HRV) is associated with positive physiological and psychological effects. HRV is affected by breathing parameters, yet debate remains regarding the best breathing interventions for strengthening HRV. The objective of the current study was to test whether the inclusion of a postexhalation rest period was effective at increasing HRV, while controlling for breathing rate. A within-subject crossover design was used with 40 participants who were assigned randomly to a breathing pattern including a postexhalation rest period or a breathing pattern that omitted the postexhalation rest period. Participants completed training on each breathing pattern, practiced for 6 min, and sat quietly during a 5-min washout period between practices. Participants were given instructions for diaphragmatic breathing at a pace of six breaths/minute with or without a postexhalation rest period. Recordings of heart rate, breathing rate, HF-HRV, RMSSD, LF-HRV, and SDNN were collected before and during each of the breathing trials. HRV indices were derived from Lead 1 ECG recordings. Pairwise contrasts showed that inclusion of a postexhalation rest period significantly decreased heart rate (p<.001) and increased HF-HRV (p<.05). No differences were found for breathing rates (p>.05), RMSSD (p>.05), and SDNN (p>.05). Results indicated that omission of the postexhalation rest period resulted in higher LF-HRV (p<.05). A postexhalation rest period improves HF-HRV, commonly associated with self-regulatory control, yet the importance of a postexhalation rest period requires further exploration.

Journal Reference:

Russell MEB, Scott AB, Boggero IA, Carlson CR. Inclusion of a rest period in diaphragmatic breathing increases high frequency heart rate variability: Implications for behavioral therapy. Psychophysiology, 2017;54:358 – 365.

Controlled breathing lowers sympathetic activity, even when performed at a relatively fast pace

Key Points

• Controlled breathing reduces sympathetic activity, even when performed at a relatively fast pace

• The reduction in sympathetic activity might be due to increased focus or increased tidal volume

The Breathing Diabetic Summary

Several studies have shown the positive effects of slow, controlled breathing.  For example, Oneda et al. (2010) showed that slow breathing reduced blood pressure, heart rate, and sympathetic activity in hypertensive patients.  A study published in Nature showed that slow breathing increased autonomic function, arterial function, and blood oxygen saturation in type 1 diabetics.

However, in most studies looking at controlled breathing, the breathing rate is controlled and reduced.  The current study examined the role of the “controlled” part.  That is, are the benefits due to controlling respiration or slowing it down?

To do this, they had participants breathe both spontaneously and at a controlled pace of 12 breaths/min.  A rate of 12 breaths/min was chosen because it is a “typical” breathing rate given in most physiological textbooks.

They found that the controlled breathing lowered sympathetic activity, but it did not lower blood pressure.  Thus, this relatively “fast” pace compared to other studies (typically 6 breaths/min) still lowered sympathetic activity.

Interestingly, several patients actually had a slower spontaneous breathing rate (~5-9 breaths/min) than the controlled pace.  But, even in these patients, their sympathetic activity was lowered when they switched to the controlled pace.  This suggests that there is a “meditative/focus” aspect of controlling your breath that relaxes you and lowers sympathetic activity.

Overall, this study shows that simply controlling your breathing rate can lower sympathetic activity.  Therefore, if you are not yet able to drop into the 4-6 breaths/min range (which is usually suggested), there are still benefits to using an app to control your breathing rate at a pace that is comfortable to you. 

Abstract

Controlled or paced breathing is often used as a stress reduction technique but the impact on blood pressure (BP) and sympathetic outflow have not been consistently reported. The purpose of this study was to determine whether a controlled breathing (12 breaths/min, CB) rate would be similar to an individual’s spontaneous breathing (SB) rate. Secondly, would a CB rate of 12 breaths/min alter heart rate (HR), BP, and indices of muscle sympathetic nerve activity (MSNA). Twenty-one subjects (10 women, 11 men) performed two trials: SB, where the subject chose a comfortable breathing rate; and CB, where the subject breathed at a pace of 12 breaths/min. Each trial was 6 min during which respiratory waveforms, HR, BP (systolic, SBP; diastolic, DBP), and MSNA were recorded. During CB, the 6 min average breathing frequency (14±4 vs 12±1 breaths/min, P<0.05 for SB and CB, respectively), MSNA burst frequency (18±12 vs 14±10 bursts/min, P<0.01) and MSNA burst incidence (28±19 vs 21± 6 bursts/100 heart beats, P<0.01) were significantly lower than during SB. HR (66±9 vs 67±9 beats/min, P<0.05) was higher during CB. SBP (120±13 vs 121±15 mmHg, P=0.741), DBP (56±8 vs 57±9 mmHg, P=0.768), and MSNA total activity (166± 94 vs 145±102 a.u./min, P=0.145) were not different between the breathing conditions. In conclusion, an acute reduction in\ breathing frequency such as that observed during CB elicited a decrease in indices of MSNA (burst frequency and incidence) with no change in BP.

Journal Reference:

McClain SL, Brooks AM, Jarvis SS. An acute bout of a controlled breathing frequency lowers sympathetic neural outflow but not blood pressure in healthy normotensive subjects. Int J Exerc Sci. 2017;10(2):188-196.

Hypoxia has positive impacts on insulin and blood glucose levels while also increasing energy expenditure

Key Points

• Hypoxia positively impacts insulin and blood glucose while also increasing energy use

• Hypoxia and exercise combined reduce weight and blood pressure in obese patients

• The positive effects of hypoxia are dose-dependent

Breathing Blueprint Summary

I love review studies because they save us a lot of time.  Researchers go through all of the literature on a specific topic and consolidate everything into one place for us to read. I like to think of The Breathing Diabetic as a big review of all of the research on breathing, health, and well-being…

This paper reviewed the literature on the potential therapeutic benefits of hypoxia for obese individuals.  We know from other papers we have reviewed on hypoxia that there are many benefits for diabetics as well.  And, since diabetes and obesity often occur simultaneously, this review study is relevant for us.

One important point they make, which bears repeating, is that it is not feasible for us all to have access to high altitude.  We cannot simply move to the mountains, or somewhere close enough, to periodically expose ourselves to high altitude.  But, there are ways to experience some of the effects of altitude while at sea level.  The authors specifically mention masks and tents that can reduce the amount of inspired oxygen to simulate high altitude.  However, we cannot forget that breath holds also simulate high altitude and are available to us anytime, for free!

One of the key findings was that fasting blood glucose and insulin levels were reduced in animals following intermittent hypoxia.  Additionally, energy expenditure was increased in animals following hypoxic exposure.  Finally, hypoxia combined with exercise (what they called “active hypoxia”) decreased body weight and blood pressure in obese humans.

They also found contradictory results in some studies, which appeared to be due to the severity of the hypoxia protocol used (something we have reviewed previously). Thus, again we see that the benefits of hypoxia are dose-dependent.

Overall, the authors conclude that hypoxia could be beneficial for obese populations. However, the improvements in insulin, blood glucose, weight, and blood pressure shown here are further evidence that intermittent hypoxia (Principle 3) can benefit anyone looking to improve overall health and well-being.

Abstract From Paper

Normobaric hypoxic conditioning (HC) is defined as exposure to systemic and/or local hypoxia at rest (passive) or combined with exercise training (active). HC has been previously used by healthy and athletic populations to enhance their physical capacity and improve performance in the lead up to competition. Recently, HC has also been applied acutely (single exposure) and chronically (repeated exposure over several weeks) to overweight and obese populations with the intention of managing and potentially increasing cardio-metabolic health and weight loss. At present, it is unclear what the cardio-metabolic health and weight loss responses of obese populations are in response to passive and active HC. Exploration of potential benefits of exposure to both passive and active HC may provide pivotal findings for improving health and well being in these individuals. A systematic literature search for articles published between 2000 and 2017 was carried out. Studies investigating the effects of normobaric HC as a novel therapeutic approach to elicit improvements in the cardio-metabolic health and weight loss of obese populations were included. Studies investigated passive (n = 7; 5 animals, 2 humans), active (n = 4; all humans) and a combination of passive and active (n = 4; 3 animals, 1 human) HC to an inspired oxygen fraction (FIO2) between 4.8 and 15.0%, ranging between a single session and daily sessions per week, lasting from 5 days up to 8 mo. Passive HC led to reduced insulin concentrations (-37 to -22%) in obese animals and increased energy expenditure (+12 to +16%) in obese humans, whereas active HC lead to reductions in body weight (-4 to -2%) in obese animals and humans, and blood pressure (-8 to -3%) in obese humans compared with a matched workload in normoxic conditions. Inconclusive findings, however, exist in determining the impact of acute and chronic HC on markers such as triglycerides, cholesterol levels, and fitness capacity. Importantly, most of the studies that included animal models involved exposure to severe levels of hypoxia (FIO2 = 5.0%; simulated altitude >10,000 m) that are not suitable for human populations. Overall, normobaric HC demonstrated observable positive findings in relation to insulin and energy expenditure (passive), and body weight and blood pressure (active), which may improve the cardio-metabolic health and body weight management of obese populations. However, further evidence on responses of circulating biomarkers to both passive and active HC in humans is warranted.

Journal Reference:

Hobbins L, Hunter S, Gaoua N, Girard O. Normobaric hypoxic conditioning to maximize weight loss and ameliorate cardio-metabolic health in obese populations: a systematic review. Am J Physiol Regul Integr Comp Physiol. 2017;313:R251-R264.

Breathing center in brain has powerful effects on higher-order brain functions

Key Points

• The breathing center in the brain has a powerful effect on higher-order brain functions

• Slow and regular breathing promotes calmness, where as rapid breathing promotes arousal

The Breathing Diabetic Summary

Anytime a study gets featured in Science, we know it’s time to sit up straight and read closely.  This paper is no exception.   

The first observation they made was that slower breathing was associated with calm behaviors, whereas faster breathing was associated with active behaviors. This sounds obvious, but it gets interesting.

They found that if they removed a certain cluster of brain neurons (Cdh9/Dbxl preBotC), they were able to turn off this active mode, and subsequently promote slow breathing and calm behaviors.  Thus, they isolated the exact cluster of brain neurons that promote an active, aroused state. Interestingly, these neurons are also controlled by breathing.  What’s more, the authors showed that these “breathing neurons” are a gateway to the rest of the brain, helping explain how slow breathing is able to calm you down.

What does this mean for us?  Essentially, their results show that we can calm ourselves by breathing slow, or excite ourselves by breathing fast, something we probably already knew by now.  However, they are showing the exact set of neurons controlling this process and showing that these neurons give the breath “direct access” to higher-order brain function.  That’s pretty amazing and definitely Science worthy.

Abstract

Slow, controlled breathing has been used for centuries to promote mental calming, and it is used clinically to suppress excessive arousal such as panic attacks. However, the physiological and neural basis of the relationship between breathing and higher-order brain activity is unknown.We found a neuronal subpopulation in the mouse preBötzinger complex (preBötC), the primary breathing rhythm generator, which regulates the balance between calm and arousal behaviors. Conditional, bilateral genetic ablation of the ~175 Cdh9/Dbx1 double-positive preBötC neurons in adult mice left breathing intact but increased calm behaviors and decreased time in aroused states. These neurons project to, synapse on, and positively regulate noradrenergic neurons in the locus coeruleus, a brain center implicated in attention, arousal, and panic that projects throughout the brain.

Journal Reference:

Yackle K, Schwarz LA, Kam K, Sorokin JM, Huguenard JR, Feldman JL, Luo L, Krasnow MA. Breathing control center neurons that promote arousal in mice. Science. 2017;355(6332):1411-1415.

Slow breathing improves autonomic function in type 1 diabetics

Key Points

• Slow breathing increased autonomic function, arterial function, and blood oxygen saturation in type 1 diabetic patients

• Slow breathing stimulates the parasympathetic nervous system and suppresses the sympathetic nervous system, providing an antioxidant effect

• “Slow breathing could be a simple beneficial intervention in diabetes.”

Breathing Blueprint Summary

The last key point above, taken directly from the abstract, says it all. This paper was published in Nature, one of the most prestigious scientific journals around, and they are highlighting the usefulness of slow breathing for diabetes and autonomic function in general.  Pretty awesome.

Diabetics suffer from an enhanced risk for cardiovascular disease, which is associated with autonomic dysfunction.  However, slow breathing has been shown to restore autonomic balance, suggesting that it might be applicable in type 1 diabetes.

Participants in the study performed 5 minutes of spontaneous breathing, followed by 2 minutes of slow breathing at 6 breaths/min.  That is a very short amount of time, yet they still got fairly remarkable results. 

During spontaneous breathing, diabetics had worse baseline data than controls.  For example, diabetics had a lower resting blood oxygen saturation and higher blood pressure.  The main marker of autonomic function that they measured was the baroreflex sensitivity (BRS). BRS measures your body’s ability to quickly adjust your blood pressure to match the current circumstances.  At baseline, the diabetics’ had a lower BRS score.

However, after just 2 minutes of slow breathing, their BRS increased to values similar to those of the controls during spontaneous breathing.  The authors believe this occurred due to a reduction in sympathetic nervous system activity and an increase in parasympathetic activity.

They also provide evidence that this shift in autonomic activity has a direct antioxidant effect.  Because diabetics (and really anyone with a chronic disease) suffer from excess oxidative stress and free radicals, this aspect of slow breathing is extremely important for improving our overall health and well-being.

Lastly, slow breathing also improved the arterial function and blood oxygen saturation of the diabetics. The authors suspect the improvements in oxygen saturation were due to improved ventilation perfusion (i.e., better matching of air and blood flow in the lungs). 

In summary, with only 2 minutes of slow breathing, type 1 diabetics were able to improve autonomic function, enhance antioxidant capacity, and improve blood oxygen saturation. These results provide practical evidence that slow breathing can improve the overall health of diabetics.

Abstract from Paper

Hyperoxia and slow breathing acutely improve autonomic function in type-1 diabetes. However, their effects on arterial function may reveal different mechanisms, perhaps potentially useful. To test the effects of oxygen and slow breathing we measured arterial function (augmentation index, pulse wave velocity), baroreflex sensitivity (BRS) and oxygen saturation (SAT), during spontaneous and slow breathing (6 breaths/min), in normoxia and hyperoxia (5 L/min oxygen) in 91 type-1 diabetic and 40 age-matched control participants. During normoxic spontaneous breathing diabetic subjects had lower BRS and SAT, and worse arterial function. Hyperoxia and slow breathing increased BRS and SAT. Hyperoxia increased blood pressure and worsened arterial function. Slow breathing improved arterial function and diastolic blood pressure. Combined administration prevented the hyperoxia-induced arterial pressure and function worsening. Control subjects showed a similar pattern, but with lesser or no statistical significance. Oxygen-driven autonomic improvement could depend on transient arterial stiffening and hypertension (well-known irritative effect of free-radicals on endothelium), inducing reflex increase in BRS. Slow breathing-induced improvement in BRS may result from improved SAT, reduced sympathetic activity and improved vascular function, and/or parasympathetic-driven antioxidant effect. Lower oxidative stress could explain blunted effects in controls. Slow breathing could be a simple beneficial intervention in diabetes.

Journal Reference:

Bernardi L, Gordin D, Bordino M, Rosengård-Bärlund M, Sandelin A, Forsblom C, Per-Henrik Groop PR. Oxygen-induced impairment in arterial function is corrected by slow breathing in patients with type 1 diabetes. Sci Rep. 2017;7:6001. DOI:10.1038/s41598-017-04947-4.