Diabetes and the Heart: Cardiomyopathy, Energy Utilization, and Ketosis


Obesity and diabetes are rampant — more than 40% of adults in the US are obese and approximately 1 in 10 have diabetes (1). An even greater number have “prediabetes”, indicating a large majority of adults are metabolically unhealthy. These conditions are sometimes considered twin epidemic s—  as they can (and often do) occur in conjunction. While neither are necessary nor sufficient for the other to occur, the metabolic causes and consequences often overlap.

We usually think of obesity and diabetes in their metabolic terms — using phrases like high blood glucose, insulin resistance, and body fatness to typify them. However, both diseases can have profound adverse effects on the cardiovascular system in addition to their metabolic consequences.

One of the primary findings in both obesity and diabetes is something called cardiomyopathy — a disease of the heart muscle. One manifestation of this is what is known as left-ventricular diastolic dysfunction, in which the main pumping chamber of the heart (the left ventricle, or LV) loses its ability to relax. Relaxation (diastole) is necessary for our heart to fill with blood before contraction (systole) ejects the blood out of the aorta and into our circulation.

The obese/diabetic heart has reduced ability to relax, and therefore doesn’t fill properly. In turn, this can lead to systolic dysfunction — a reduced ability to contract and eject blood. The dangerous cycle of diastolic and systolic dysfunction makes it so that circulation in the heart is drastically impaired.

This loss of function is accompanied by some pretty major structural changes to the heart. Diabetes and obesity can cause the walls of the heart to thicken — termed cardiac hypertrophy. These thick, muscular walls lose some of their elastic ability. Stiffer walls are worse at contracting and relaxing. Wall thickening occurs because individual heart cells (known as cardiomyocytes) actually grow larger themselves. As each cell grows (hypertrophies), the wall thickens in proportion.

Ventricle size also increases in diabetic and obesity cardiomyopathy, expanding in size and volume. This process is known as dilatation, and most often occurs in the left ventricle, though the right ventricle also experiences dilatation to some degree.

A final structural change involves a process known as fibrosis. Fibrosis of the heart is implicated in the process of thickening and stiffening. Our heart muscle is surrounded by a tissue layer called the extracellular matrix (ECM) — which is composed of proteins like collagen and elastin, vascular cells, and other immune and fibrotic cells that serve as a structural scaffold for the heart. In diabetes and obesity, the heart ECM becomes fibrotic  —  an abnormal amount of ECM accumulates and/or the composition changes; leading to a stiffer, fibrotic heart.

This structural remodeling is bad news for the heart. A large ventricle size may prevent adequate contraction, and thicker, stiffer walls prevent adequate contraction and relaxation, which is further impaired by fibrosis. As a result, the heart becomes less efficient at pumping blood, eventually leading to heart failure.

Normal (top) and hypertrophied/fibrotic heart (bottom) Source: Herum KM, Lunde IG, McCulloch AD et al. J Clin Med 2017

What causes  these changes? Some of the pathophysiology is specific to either obesity or diabetes, but a lot of the mechanisms are shared.

In obesity, one of the primary causes of left ventricular hypertrophy is an increased load on the heart. Obese individuals have a higher metabolic activity and increased lean/fat mass, and this increases total blood volume and a hypercirculatory state. An increase in blood volume means that the heart experiences a greater filling volume and elevated systolic and diastolic pressure. The heart must also work harder (i.e. generate more force) to eject blood against these increased pressures. This means that the left ventricle work rate and wall stress are increased, leading to a thicker, hypertrophied muscle. The heart, just like a biceps or triceps muscle, grows larger with “training.”

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Increased wall stress and elevated ventricular work rate means the heart has a higher demand for oxygen. In diabetes and obesity, as we will see later, oxygen supply may be reduced and therefore, the heart may be “starved” of oxygen.

Obesity and diabetes are often characterized by insulin resistance — the muscles and other tissues in the body fail to respond properly to insulin, and therefore blood glucose uptake and utilization is impaired. Insulin resistance leads to hyperglycemia, or high blood glucose. High blood glucose (blood sugar) can wreak havoc on the cardiovascular system — it increases oxidative stress and inflammation, reduces blood vessel function, and can lead to the production of advanced-glycation end products (AGEs). AGEs can be thought of as “sticky” molecules that attach to and cross-link proteins in the body, altering their function.

Insulin resistance also leads to a metabolic shift in the heart. Normally, the heart metabolizes glucose (also fatty acids, lactate, and ketone bodies) as a fuel substrate. Without proper insulin action, however, glucose can’t be transported into the myocytes.

Thus, the heart shifts from glucose oxidation to primarily fatty acid oxidation. For one, this increases the oxygen demand of the heart, since fatty acids require more oxygen for their metabolism than does glucose. Secondly, an increased flux of fatty acids into the myocytes can lead to something known as lipotoxicity and dyslipidemia; when supply of these molecules outpaces demand or utilization. Toxic byproducts of fatty acids and triglycerides can promote myocyte cell death and cardiac dysfunction.

Pathways of fatty acid and glucose metabolism in the heart. Source: Radcliffecardiology.org

Inflammation — characterized by increased presence of proinflammatory cytokines in the heart, is also elevated in both obesity and diabetes. This can be due to hyperglycemia, insulin resistance, or increased production of inflammatory cytokines from adipose (fat) tissue. Inflammation contributes in part to the cardiac hypertrophy and fibrosis involved in cardiac dysfunction.

A final shared mechanism among obesity and diabetes is overactivation of neurohumoral systems; including the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS).

In the body, the RAAS has several effects — causing vasoconstriction of blood vessels and sodium/fluid retention in order to maintain blood pressure. The main actor here is angiotensin II (ANG II), which causes these effects by binding to its receptors which are present throughout the cardiovascular system.

RAAS is overactive in obesity and diabetes. Several components of RAAS are found in high quantities in adipose tissue, meaning obese individuals have higher levels of angiotensin II than normal-weight individuals (even those with hypertension or cardiomyopathy). In diabetes, RAAS is also overactivated due to hyperglycemia, insulin resistance, and other factors.

When RAAS is chronically overactive, it has adverse effects including vasoconstriction of blood vessels, stimulation of reactive oxygen species (ROS), cell proliferation, and fibrosis. Angiotensin II is actually a pro-growth factor in the cardiovascular system, and high levels can promote cardiac hypertrophy.

Increased RAAS and insulin resistance can also lead to SNS activation. In the cardiovascular system, SNS activation induces many of the same pathways as does RAAS, including vasoconstriction, inflammation and oxidative stress, and cell proliferation.

One final common pathway involved in cardiomyopathy in obesity and diabetes involves endothelial dysfunction. Normally, our blood vessels regulate blood flow and pressure through vasoconstriction and vasodilation (relaxation). A healthy balance of molecules that promote dilation (nitric oxide, NO) and constriction (endothelin-1, ET-1) fine-tunes vascular tone to meet our metabolic needs. Many of the above mechanisms (RAAS, inflammation, hyperglycemia, SNS activation) can impair endothelial function. While it contributes to cardiomyopathy, endothelial dysfunction is also implicated in the progression of atherosclerosis, and has other effects such as reducing exercise capacity and cognitive function.

While these are only some of the mechanisms behind cardiomyopathy resulting from obesity and diabetes, the description illustrates a complex interaction between metabolic diseases and the cardiovascular system.

Let’s now switch from discussing structural abnormalities in the diabetic/obese heart to some functional changes that occur, in particular those related to energy metabolism. Specifically, there are some interesting new perspectives on the “inefficiency” of the diabetic heart related to its metabolism (or lack thereof) of ketone bodies. This is highly relevant given that ketogenic diets have long been prescribed as a treatment for diabetes.

We mentioned earlier that, due to insulin resistance, the diabetic heart can undergo a metabolic shift to favor the breakdown of fatty acids as a fuel source. In diabetes, ketone body production by the liver and uptake of ketone bodies by the heart is often elevated. Initially, this would seem beneficial, as ketone bodies (including beta-hydroxybutyrate or BHB) are very efficient energy sources. However, animal data seem to suggest that the diabetic heart is still energy inefficient despite a high uptake of ketone bodies.

This inefficiency may occur because the process of producing ketone bodies (ketogenesis) and breaking down ketone bodies to produce energy (ketolysis) are inherently opposite processes — you can’t have high levels of both in a single organ such as the heart. In type 1 and type 2 diabetes, it appears that the breakdown of ketone bodies is reduced — either due to an increase in ketogenesis (type I diabetes) that inhibits ketolysis or a decrease in enzymes responsible for the breakdown of ketones (type 2). Low levels of insulin in type 1 diabetes promote increased ketone body production. High levels of insulin in type 2 diabetes (insulin resistant diabetes) reduce ketogenesis and also lower levels of ketolytic enzymes.

Here is a nice list of differences in the type 1 and type 2 diabetic heart that appears in a recent commentary article on the diabetic heart and energy (in)efficiency.

Type 1 diabetes

  • Low levels of insulin
  • High levels of ketone bodies (10-fold vs. non-diabetic heart)
  • Increased levels of ketogenesis enzymes
  • Reduced levels of ketolysis enzymes

Type 2 diabetes

  • High levels of insulin
  • Lower levels of ketone bodies vs. type I diabetes
  • No change in ketogenesis enzymes vs. a non-diabetic heart
  • Reduced levels of ketolysis enzymes

These metabolic abnormalities make it so that the diabetic heart can’t utilize ketone bodies for energy — at least not as well as a non-diabetic heart. Given the fact that glucose utilization is also impaired (due to low levels of insulin or insulin resistance), we have a situation where the diabetic heart is essentially “starved” of energy. As mentioned earlier, fatty acids are still an available source of energy, but these require more oxygen and highly-functioning mitochondria for adequate energy provision — something the diabetic heart also lacks. Indeed, mitochondrial dysfunction is also a characteristic of both type 1 and type 2 diabetes.

Why is all of this important? Well, to design treatment strategies targeting diabetes and in particular the diabetic heart, it’s useful to know the mechanisms of dysfunction. These data would suggest that ketogenic diets may NOT be useful for improving cardiac efficiency in the diabetic heart. Ketogenic diets are effective for improving weight/body fat and insulin sensitivity in people with diabetes, to be sure. However, from a cardiovascular perspective, the above discussion suggests that ketogenic diets may be not as useful for improving cardiac energetics due to a couple of reasons including:

  1. Ketone levels in diabetes are already high, and increasing levels further via a ketogenic diet may not improve the heart’s utilization of ketones or energetic efficiency.
  2. Ketolysis enzymes are reduced in diabetes and therefore increased ketone bodies will not lead to greater utilization of these ketones.

This brings up another interesting discussion about the use of exogenous ketones in people with diabetes. Exogenous ketones (ketone “supplements”) are a very popular research area right now, as they’ve been shown to improve aspects of athletic performance, cognition, aging, and may even be a potential countermeasure/supplement for cardiovascular health. The latter application relates to the fact that the heart can and will use ketones if they are provided. This may only apply to a “healthy” heart (a non-diabetic heart) given what we have just discussed, and suggests they may not have any application for diabetes. This is definitely an area that needs more research, however.

What can be done to improve health and energetics of the diabetic heart? That brings us to exercise. While the data on exercise in diabetes is beyond the scope of this post, it is well known that both aerobic and resistance exercise can benefit diabetes by improving weight and body composition, increasing insulin sensitivity and, relevant to our discussion today, likely improve cardiac efficiency and mitochondrial function. Together, exercise can increase the “efficiency” of the diabetic heart by allowing it to access more metabolic substrates through multiple different mechanisms.

All of life is energy, and how we use or misuse it has a profound effect on health.

Could Alternate-Day Fasting Help Prevent Age-Related Frailty and Cognitive Decline?


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“Anti-aging” is a phrase I use yet somewhat despise. Nothing is really “anti-aging” — we can’t pause the forward motion of time; whether we speak of time in a biological or chronological sense. All of us are aging by the second. What can be altered, however, is the rate at which we age, and there is good evidence that several different interventions such as exercise, a “healthy” diet, and stress management, can all be effective.

Another method to slow aging includes dietary manipulation, and a popular dietary intervention known as intermittent fasting (IF) is promising and extremely popular. IF is a broad term though and can include iterations such as time-restricted feeding (TRF), 5:2 fasting, weekly 24-48-hour fasts, or another popular form known as every-other-day (EOD) fasting.

Why IF is so popular relates to the fact that it is an “easy” and effective way to reduce caloric intake. Calorie restriction without malnutrition is one of the best-known ways to slow aging (in animals, at least) but is somewhat hard to do — many individuals find that constantly restricting their food intake is unpleasant. It seems that some prefer to use a fasting window to limit their calorie intake at certain times of the day/week, allowing them to eat what they would otherwise like during their “feeding window.”

EOD fasting involves consuming food one day, fasting the other, and repeating. The simple framework and potential effectiveness has led to EOD being looked at for its effects on several health outcomes — aging and longevity perhaps being the most heavily investigated areas.

A new study published in the journal Geroscience aimed to determine the effects of EOD fasting on indices of frailty — which is defined as an “age-related loss of physiological reserve [and]…increased susceptibility to various internal and or external stressors leading to poor health outcomes or death.”

The time of intervention was a key part of this study. Many previous investigations have chosen to initiate a fasting regimen early in life, yet the benefits of fasting implemented later in life are less well-known. Can one start fasting in their 60s, 70s, or 80s and still reap the benefits?

Brief study methods

This study used male and female mice to investigate the effects of fasting on age-related frailty measures and to determine whether a sexual dimorphism exists in these effects. I.e. — does late life-initiated fasting affect males and females differently?

Mice in this study were put on their respective dietary intervention starting at 20 weeks of age, prior to which they had been fed a standard chow diet. The interventions included:

Ad libitum dietary intervention: mice were given unrestricted (ad libitum) access to standard rodent chow throughout the study.

Every-other-day fasting (EOD) intervention: mice alternated days of ad libitum access to standard rodent chow (fed days) and complete removal of food access for 24 hours (fast days.) In other words, they ate every other day and fasted every other day.

Before, during, and after each dietary intervention, outcomes related to frailty were measured and analyzed separately for each sex. The measures included a variety of physical, biological, and cognitive outcomes including: food intake, body weight, % fat mass and % lean mass, fasting blood glucose and glucose tolerance, insulin levels, metabolic rate (oxygen consumption and carbon dioxide production), respiratory exchange ratio (RER; an indicator of what fuels the body is using), short-term and long-term memory, forelimb grip strength, neuromuscular coordination, hydrogen sulfide (H2S) production, and inflammatory cytokine gene expression.


As mentioned earlier, analysis of the data was done in a sex-dependent manner, meaning all outcomes were analyzed separately for males and females. Results were compared within each group at each time point (i.e. post-intervention vs. baseline) as well as between each group at all time points (EOD fasting vs. ad libitum fed groups.)

  • Food consumption: the male EOD group reduced overall food consumption by ~38% compared to the ad libitum fed group. Female EOD mice did not reduce food consumption significantly compared to the ad libitum fed mice.
  • Body weight and body composition: the male EOD mice reduced their body weight throughout the intervention, largely driven by a reduction in fat mass. Female EOD mice lost weight up until day 47 (of 78) of the intervention, but body weight did not change thereafter, nor did body composition.
  • Metabolism: EOD fasting did not affect circadian rhythmicity of heat/energy production, oxygen consumption/carbon dioxide production, or heat production.
  • Metabolic flexibility: EOD led to an increase in “metabolic flexibility” — an ability to shift from fatty acid to carbohydrate oxidation and vice-versa — with the observed effect being larger in female than male mice.
  • EOD fasting improved fasting blood glucose and glucose handling in male (~33%) and female (~20%) mice.
  • Musculoskeletal health: male EOD mice improved their relative grip strength compared to ad libitum fed mice, while female EOD mice experienced no improvement in grip strength.
  • Motor coordination and balance improved in male, but not female, EOD mice.
  • Cognitive health & performance: EOD fasting improved some aspects of short-term and long-term hippocampal-dependent memory in male but not female mice.
  • EOD fasting reduced age-related anxiety and prevented age-related declines in ambulatory behavior (movement) in male mice, but not female mice.
  • Hydrogen sulfide production: hydrogen sulfide production in the kidney was enhanced in male EOD mice, but female EOD mice experienced no change in hydrogen sulfide production
  • Inflammation: EOD fasting reduced levels of some pro-inflammatory cytokine genes in the brain and increased gene expression of a neuroprotective protein known as DJ-1.

A lot of results presented here, but that is definitely one of the strengths of this study. Albeit conducted in a rodent model of aging, this investigation nonetheless provided a comprehensive suite of measurements that have been shown to relate to frailty in mice/rats AND humans. Indeed, the authors do mention how many of the frailty indices utilized in this study have correlates in humans.

Frailty is not a single-measure “syndrome” but rather, an age-related phenomenon that affects all bodily systems including musculoskeletal, cardiovascular, neurohormonal, and nervous, among others. The aim of this study was to investigate the effects of fasting on frailty as a whole entity, and this was accomplished by including biological, cognitive, and performance outcomes into the study design.

Some of the most interesting outcomes, from my point of view, are probably those related to glucose handling, strength/body composition, and the tests of short- and long-term memory. As many are aware, aging brings with it a decline in metabolic health, strength, lean muscle mass, and a drastic reduction in cognitive abilities. To be sure, the declines can be prevented by regular training and maintenance of these systems and don’t happen to everyone. The fact that a regimen of EOD fasting could also prevent (but perhaps not improve) a decline in these measures is very promising. Paired with an exercise and cognitive training regimen, this could make for a potent “anti-aging” stack.

The big question in the study is why female mice did not experience many of the benefits of EOD that were observed in male mice. This all really comes down to energy intake. Many (if not most) of the benefits of any intermittent fasting regimen probably boil down to the fact that this is simply an easier way to reduce overall energy intake. Compared to continuously restricting calories, fasting seems to be more feasible. The female mice in this study failed to reduce their overall energy intake to a considerable degree compared to the ad libitum fed mice, even though they were restricted from consuming any food on half of the study days. This was driven by a massive overconsumption of calories on the fed days (almost twice as much as the control mice.)

For intermittent fasting (specifically EOD fasting) to exert many of its benefits, it seems that complete caloric compensation must be avoided. The energy deficit (which was 30-40% in this study) is what drives many of the beneficial adaptations and protections against aging, or at least that is what can be concluded from the results of this investigation. When the body experiences stress (such as nutrient or energy deprivation) even for a short while, beneficial adaptations take place that make the body more resilient. This is a concept known as hormesis, and applies as much to diet as it does to exercise.

Moral of the story. To slow or prolong aging, it might not matter HOW one chooses to limit their energy intake, just that they do, at least intermittently. Whether this comes from eating one meal a day, every-other-day fasting, or daily time-restricted feeding matters not, and the “diet” utilized may just depend on your willingness or interest to try out any one of the nearly limitless dietary interventions for health and longevity.

Study cited

Henderson YO, Bithi N, Link C, et al. Late-life intermittent fasting decreases aging-related frailty and increases renal hydrogen sulfide production in a sexually dimorphic manner. GeroScience. 2021;43(4):1527-1554.

Combining Time-Restricted Eating with Exercise Enhances Fat Loss


Intermittent fasting is a recent health trend touted for its proven and hypothetical benefits for weight loss, aging, cognitive health, and metabolism. Many studies — in animals and humans — have provided strong evidence that the risk for several diseases can be reduced through various forms of intermittent fasting.

One form of intermittent fasting, known as time-restricted eating (TRE) is probably even more popular because it is generally easy to adopt, less restrictive than other forms of fasting or dietary calorie restriction, and straightforward. With TRE, one consumes all of their daily calories within a predefined “eating window.” Most commonly, TRE takes the form of a 16:8 fast or 18:6 fast, where 16 or 18 hours are spent fasting each day, with the remaining 8 or 6 hours allocated for the eating window. Other than the timing, no “restrictions” are placed on the amount or types of food consumed.

Like intermittent fasting, TRE is also beneficial for numerous health outcomes. TRE is now popular among athletes who are looking to simultaneously lean out, build muscle, and improve performance. But improving body composition, strength, and aerobic fitness is also a relevant public health goal, as obesity levels rise and metabolic health declines throughout the world.

Physiological effects of fasting on numerous body tissues and organs. Source: de Cabo et al. 2019

In this case, whether TRE could be a useful dietary strategy to reduce body fat is an important question. Many traditional diets fail for various reasons, and TRE may represent a way to sidestep this barrier to adherence. Furthermore, very few studies have combined TRE with an exercise regimen to determine if this may further enhance weight/fat loss and help to promote lean muscle building, especially among metabolically unhealthy (i.e. overweight or obese) individuals.

A study published in Physiological Reports investigated the question of whether TRE may be an effective dietary strategy to reduce fat mass while preserving lean mass (fat-free mass) in inactive overweight and obese adults, and whether TRE + exercise would improve biomarkers of cardiometabolic health, hormone profiles, muscle performance, and alter dietary intake.

Brief study methods

21 physically inactive adults who were characterized as being overweight or obese (BMI betweeen 25 and 34.9 kg/m2) completed this study. I’ll note here that 18 of the participants were female, while just 3 were male.

Participants were randomly assigned to one of two groups: a time-restricted eating (TRE) group — who were told to practice a 16:8 TRE regimen (eat between 12pm and 8pm each day) or a normal eating (NE) group — who were given no guidance on when to eat.

For 8 weeks, participants adhered to their prescribed eating regimen while also engaging in a progressive combined aerobic + resistance exercise training program. The program consisted of 3 days per week of strength training, which included various upper- and lower-body exercises, with at least 48 hours between each strength training session.

The aerobic exercise component involved gradually increasing the duration of exercise each week beginning with 75 minutes (week 1) and adding 75 minutes each week until week 5 (to hit a target goal of ~300 minutes per week.) The intensity of exercise was at >55% of heart-rate reserve (to calculate heart-rate reserve, take your maximum heart rate – resting heart rate.)

One notable aspect of the training was that participants never completed sessions in the fasted state — the TRE group trained between 1pm and 7pm and the NE group trained between 9am and 7pm. While not ideal (I would like to see everyone train at the same time of day), this removed the confounding factor of having some participants train fasted vs. fed.

Outcomes measures included dietary adherence and caloric intake (to observe effects of diet), body mass, body fat, and lean body mass (DEXA), blood pressure and heart rate, hormones (estradiol, progesterone, testosterone, DHEA, cortisol), and cardiometabolic biomarkers including total cholesterol, HDL, LDL, insulin, high-sensitivity C-reactive protein, hemoglobin A1c, and triglycerides. 


A few things to note before going over the main findings. Overall, participants were very adherent to both the dietary regimens and the exercise training. The TRE group reported a daily eating window of ~7 hours (~17 hour fasting window) and the NE group reported a daily eating window of ~11 hours (~13 hour fasting window). Enough of a difference here to produce a likely difference in outcome measures, if they exist.

Both of the groups reduced their caloric intake throughout the study — the TRE group by 306 calories/day and the NE group by 253 calories per day. So, dietary restriction (inadvertently) occurred in both groups, despite no advice to participants to do so.

Let’s take a look at some outcomes

  • Fat mass (tissue and region) was reduced in both the TRE and NE groups, however, the reduction in fat mass and total body mass was greater in the TRE group vs. the NE group. Specifically:
    • The TRE group lost 3kg of body mass throughout the study
    • BMI dropped by 0.36 kg/m2 in the TRE group
    • Total fat mass dropped by 3% in the TRE group vs. 1% in the NE group
  • Lower body (knee) strength and endurance improved in both groups
  • Resting heart rate was reduced in both groups
  • No changes in hormones or cardiometabolic biomarkers were observed (these were only analyzed in female participants)

These results provide some very relevant information for individuals who are interested in implementing TRE into their lifestyle. — whether looking to lose weight or not.

For one, it seems possible that lean mass can be increased if you combine strength training with TRE. This is a common argument against TRE, or fasting in general — that it’s not compatible with muscle building. If you add a consistent strength training regimen and adequate energy and protein intake to a pattern of short daily fasting, lean mass growth is possible.

Furthermore, not only can one improve lean mass through TRE, but also reduce their fat mass, which improves overall body composition (i.e. % body fat). Since fasting is a great way to get the body to use its own fat stores as an energy source, the benefits for reducing fat mass are to be expected. 

Finally, at least from what we can tell from this study, TRE doesn’t necessarily impair fitness or muscle performance gains during strength and aerobic training. This study was in untrained individuals, so this puts a bit of a limitation on this conclusion — anyone is going to improve when the starting point is near zero. However, similar findings in regards to fitness and metabolic outcomes have been shown in more recreationally fit individuals and even some trained populations.

Of all the “flavors” of intermittent fasting out there, I think TRE is the one most likely to catch on and stick around for the long haul. Technically, we all do some form of TRE, just with varying lengths of fasting windows. Regimens such as 16:8 and 18:6 are trendy, but this doesn’t mean other variations may be any less effective, so I encourage you to try out a daily feeding:fasting window that works with your lifestyle and helps you feel and perform at your optimal.

I generally do a daily 16:8 fast, which sometimes creeps into the 18-20-hour fasting window on the weekend, if we have a later lunch. I find that this time window allows me to intake the energy I need while also (hopefully) gain some of the metabolic benefits of working out fasted. 

While a simple clock is really all that you need to implement this practice, I have used the Zero Fasting app for years now and find it easy, fun, and even educational to use. I encourage you to download the app and try it for yourself.

Study cited

Kotarsky CJ, Johnson NR, Mahoney SJ, et al. Time- restricted eating and concurrent exercise training reduces fat mass and increases lean mass in overweight and obese adults. Physiol Rep. 2021;9:e14868.

Supplementing with Creatine Reduces the Need for Sleep


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We all need to sleep. While how much we really need is debated, somewhere around 7-9 hours per night seems to be the “sweet spot” where health and performance are optimal — at least this is what the sleep literature would suggest.

Why we sleep is not completely understood, but one of the hypothesized reasons is that sleep allows our brain to restore energy that we use while we are awake. Our brain is always using energy (in the form of ATP), but interestingly, the brain’s metabolic rate declines during sleep. We use about 44% less glucose and consume about 25% less oxygen during non-rapid eye movement (NREM) sleep compared to when we are awake.

A buildup of a molecule called adenosine is largely responsible for our drive to sleep.

Throughout the day, adenosine levels build up in the brain. This is because adenosine is produced as a byproduct the breakdown of ATP — as we expend energy, we produce more adenosine. This buildup of adenosine increases our “sleep pressure.” Eventually, when so much adenosine builds up, we are driven to bed (this is why caffeine keeps us awake — it is an adenosine receptor antagonist and blocks the effects of adenosine).

The ATP-PCr System

Since our brain replenishes energy during sleep, this is perhaps why sleep deprivation is associated with a host of adverse cognitive outcomes including short-term performance decrements and long-term chronic conditions such as cognitive decline. If you’ve ever skipped a night of sleep, you’re well-aware that the next day you are far from your mental best. An energy emergency in the brain could be the culprit.

This brings up the question of whether preventing brain energy depletion could reduce the need for sleep? If one of the main purposes of sleep is related to brain energy replenishment, this could indeed be true.

Furthermore, could replenishing brain energy during sleep deprivation prevent some of the adverse metabolic effects or reduce the need to “recover”?

A study published in the journal Sleep Research investigated these questions.

Brief study methods

This study was conducted in rats, male Sprague-Dawley rats to be specific. 

For 4 weeks, the rats were supplemented with creatine monohydrate (Cr). Cr, often associated with weight-lifting and muscle building, also plays a large role in our body’s energy supply by regulating ATP availability, especially in the brain and muscles. During situations of high metabolic demand, a molecule called phosphocreatine (PCr) is broken down in order to synthesize ATP, which we can then use as cellular energy.

It was hypothesized that Cr supplementation, by increasing total energy availability in the brain, would reduce the need for sleep in rats. Furthermore, if Cr could prevent the energy deficit in the brain created during sleep deprivation, perhaps it would compensate for some of the effects of sleep deprivation in the brain and reduce the need for make-up sleep.

Rats were implanted with EEGs (to measure brain activity) and EMGs (to measure muscle activity), as well as a microdialysis cannula to obtain tissue samples from relevant brain areas.

At baseline, during sleep deprivation, and during recovery sleep, the rats had measures of sleep (EEG) and tissue samples performed. These same measures were repeated following 4 weeks of Cr supplementation.

– Cr supplementation increased wake time and decreased total sleep time

– Cr supplementation decreased time spent in NREM slow-wave sleep, but did not alter the amount of time spent in REM sleep

– At baseline, sleep deprivation increased “sleep pressure” in rats — shown by an increased NREM and REM sleep during the first 2 hours of recovery sleep

– Cr supplementation reduced “sleep pressure” after sleep deprivation — rats needed less NREM and REM sleep during recovery sleep vs. the baseline condition

– Creatine supplementation attenuated the increase in brain adenosine concentrations during sleep deprivation.

The novelty of this study is in showing that after 4 weeks of Cr supplementation, rats had enhanced wakefulness levels following sleep deprivation compared to baseline values. These changes in wakefulness occurred in tandem with a tendency for brain PCr levels to increase and a reduction in adenosine levels.

Providing an energy substrate (or at least a precursor) such as Cr seemed to have some sort of metabolic benefit for the brain. Perhaps by increasing the pool of high-energy phosphates, the authors speculate, Cr supplementation reduced the need for the brain to replenish these reserves through sleep — both at baseline and under conditions of sleep deprivation.

It will be interesting to see whether Cr supplementation could prevent cognitive issues in humans stemming from a lack of sleep. Cr has shown to benefit several neurological disorders including ALS, Huntington’s disease, and Parkinson’s disease. It’s even considered by some to be a nootropic (cognition-enhancing drug).

Even though Cr is shown here to reduce the need for sleep, I would limit these findings to the (rat) brain, as they likely don’t extend to the negative cardiovascular and metabolic effects of sleep deprivation. Nor do we know how these results might translate to humans. Nonetheless, these results are quite interesting.

Creatine is a generally low-cost and extremely safe supplement (often found in the form of creatine monohydrate), so it might be worth experimenting with for yourself. I know of individuals who supplement with a low dose of Cr for metabolic as well as cognitive benefits. Studies have shown good evidence that Cr may also help with sport performance.

Overall, it’s worth a shot, especially on those unwanted (or sometimes necessary) sleepless nights.

Study cited

Dworak M, Kim T, Mccarley RW, Basheer R. Creatine supplementation reduces sleep need and homeostatic sleep pressure in rats. J Sleep Res. 2017;26(3):377-385.


Using Heat to Enhance Endurance Performance and Strength Gains

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Athletes — recreational or professional — are always looking for ways to gain an edge.

Recovery technology, nutritional supplements, and training devices have all been developed to help athletes get more out of their body and their training regimen. Even those who exercise for general health can still benefit from many “performance-enhancing” devices and products.

But when it comes to improving performance, sometimes the simplest strategies can be the most effective. For a long time, we have known that heat therapy can be beneficial for health — regular sauna use or hot-water immersion (think spa or hot tub) have been shown to improve cardiovascular health by lowering blood pressure and improving blood vessel function.

Regarding exercise, heat training is known to improve endurance exercise performance by boosting plasma volume. If you’ve ever trained in the humid summers of Florida (trust me on this one), you’ll know this phenomenon quite well.

We know that muscles perform better when they’re warm — hence why we “warm up” before exercise (also to prevent injury).

This leads to a few unanswered questions regarding heat and performance. Can heat training improve on resistance training gains? Few studies have actually looked at this, as most have focused on endurance-type activity.

Second, can short-term heat application potentially improve aerobic exercise performance? If so, this could be a cheap and effective way to run faster or further in a race or workout.

At the 2021 (virtual) Experimental Biology (EB) conference, I attended two poster sessions where researchers investigated these very questions. Below is a short summary of the findings and a few key takeaways. 

Poster #1: Long-term concurrent heat stress does not improve upon performance gains by resistance training

For this study, investigators wanted to determine whether resistance training with added heat stress would have an additive effect on performance enhancement — including 1 rep max leg and bench press, 5- and 10-meter sprint time, agility, peak squat jump and ballistic pushup force, and body composition.

18 recreational athletes completed a 10-week full-body resistance training program. One group trained in thermoneutral conditions at 23C (74F) and 25% humidity and another group (the heat stress group) trained in a climate chamber at 40C (104F) and 30% humidity. Pretty toasty.


  • Leg press 1 rep max improved in both conditions
  • Relative strength improved in bench press in both groups
  • Agility improved in the HEAT group at 5 weeks (midway through), but was no different at 10-weeks compared to baseline
  • No improvements were seen in 5/10 meter sprint time or peak force
  • Total upper body and total overall muscle mass increased in both groups
  • Fat mass did not change in either group

Overall — these results demonstrate that concurrent heat stress during resistance training does not seem to have an additive effect on performance or body composition outcomes. Similar gains were seen whether participants trained in thermoneutral or hot conditions.

Poster #2: The Effects of using Deep Heat on Enhancing Aerobic Performance

Investigators in this study wondered whether applying heating cream before exercise could increase endurance capacity and/or prolong time to fatigue. Heating creams (e.g., Icy Hot), while typically used to reduce soreness and pain, have scarcely been used in this context.

9 individuals participated in this study and completed two different trials where they performed a cycling test to exhaustion. During one session, they received a placebo (inactive) cream on their skin and in another session, they received the deep heating cream application prior to exercise.


  • Deep heat cream significantly improved time to exhaustion during cycling (participants cycled for 510 seconds with the deep heat cream and 391 seconds with the placebo). 

(Thanks to author G. Balasekaran for granting me permission to use his poster in this newsletter)

This study indicates that deep heat cream application prior to exercise can improve time to exhaustion, and athletes may want to consider using this strategy to achieve optimal endurance performance.

If you’re interested in “heating up” your workout, I would consider trying either of these approaches. Training outside in the blazing summer sun — whether you’re running or pumping iron, could perhaps lead to more significant improvements. As for the acute benefits of heating creams, applying some right before you head to the gym or out for a run could allow you to workout harder or longer.

Heat can be a powerful physiological stimulus, and using it to your advantage could yield some neat benefits.

Histamines are Crucial for Exercise Training Benefits


Exercise is perhaps the strongest and most potent disease-reduction strategy that we know of. 

Aerobic, and to a lesser extent resistance exercise training causes all sorts of beneficial adaptations in our body including improved metabolic function, increased muscle mass and reduced body fat, more mitochondria, and enhanced blood vessel health.

Separately and together, these adaptations reduce our risk for chronic diseases and are likely a sure-fire way to live better and longer.

A looming question in the field of exercise physiology has been how these benefits of exercise are communicated at a cellular level. What specific molecular mechanisms mediate the integrative adaptive response to exercise?

We know that a variety of signaling molecules are released during exercise (these are termed ‘myokines’). However, might one particular system or group of molecules regulate the exercise training response to a larg(er) degree?

Perhaps. A new study published in the journal Science Advances proposes that histamines, molecules released by our immune system, might play a major, if not critical role, in transducing the benefits of exercise.

Histamines are usually talked about in reference to allergic reactions — one might take an antihistamine to reduce allergy-related symptoms. These drugs work by blocking the release of histamines, thereby reducing the immune/inflammatory responses associated with common allergens.

How do these molecules relate to exercise? It has been known for some time that a single bout of acute exercise (specifically, muscle contraction) can cause the release of histamines, and histamines also play a role in sustaining post-exercise blood flow to muscles.

Whether histamines are also responsible for mediating adaptations to long-term exercise training however, has never been investigated. Therefore, the purpose of this study was to evaluate the role of histamine signaling for exercise-training induced adaptations in a variety of body systems.

Basically, the question was: “Does blocking histamine signaling during exercise training prevent some of the adaptations to training? If so, where, and to what extent?”

Brief study methods

This study had two parts: an acute study and a chronic study.

For the acute study, participants (8) completed a single bout of cycling exercise with and without histamine receptor (H1/H2) blockade. Before and after exercise, heart rate, blood flow, and blood pressure were measured to determine the role of histamines in the post-exercise cardiovascular response.

For the chronic study, participants (20) completed 6-weeks of exercise training (3 days per week of cycling exercise). One group of participants completed training with chronic blockade of the histamine H1 and H2 receptors, and one group completed training with a placebo (i.e. no histamine receptor blockade, i.e. the control group).

Measures of exercise capacity (maximal and submax exercise performance), mitochondrial capacity and function, metabolic health (glucose tolerance and insulin sensitivity), and vascular function were assessed pre and post training, as well as halfway through the training program.



Below is a summary of some of the main study findings, grouped by outcome category.

Acute study

– Post-exercise muscle perfusion (blood flow) was significantly reduced in the H1/H2 receptor blockade group. This means that histamine signaling is important for regulating post-exercise blood flow.

Chronic study

Exercise capacity and mitochondrial function

– Maximal exercise capacity (VO2 max) improved in both groups after training

– Peak power output increased in both groups, but was higher in the control group vs. the histamine receptor blockade group

– Submaximal exercise efficiency was improved in the control group, but not in the histamine blockade group

Mitochondrial capacity was increased more in the control group vs. the histamine blockade group

Antioxidant capacity increased in the control group, but not the histamine blockade group

 Metabolic function

Blood glucose and insulin levels were improved in the control group, but not the histamine blockade group

Glucose tolerance was improved in the control, but not in the histamine blockade group

 Vascular function

– Exercise training improved leg vascular function and muscle capillary number only in the control group. The histamine blockade group experienced no exercise-related improvement in vascular function

– Expression of the enzyme responsible for producing nitric oxide (NO) was increased in the control group, but not the histamine blockade group

I presented a lot of results here, so let’s summarize the findings with a few key points from the paper:

1. Histamines play an essential role in mediating the improvements in mitochondrial and antioxidant capacity in response to exercise training.

2. Exercise-induced metabolic adaptations in glucose control and insulin action are partially dependent on histamine signaling.

3. Histamines are necessary for the exercise-induced improvements in vascular function, muscle capillary content, and eNOS enzyme levels.

This is probably one of the most interesting papers that I’ve read in quite some time, for a couple of reasons.

First of all, much talk around exercise lately has centered around the ‘proteomic’ response to exercise. New techniques have allowed us to quantify the molecular response to exercise, revealing that thousands of unique molecules are released in response to a single exercise bout. 

To see evidence of significant impairments in exercise adaptations when just one signaling cascade (in this case, histamine H1/H2 signaling) is blocked is pretty noteworthy and, to be honest, quite surprising.

Secondly, this can (re)stimulate a discussion about drug development. “Exercise mimetics” are (in theory) pills that we could take to ‘mimic’ the effects of exercise. If histamines play such a role in the integrative exercise response, perhaps a histamine receptor-stimulating drug, or a cocktail containing such ingredients, could be used therapeutically to boost health and function in people unable (or unwilling) to exercise.

I’m not hopeful that we will ever have “exercise in a pill” — it just doesn’t seem reasonable (or preferable, for that matter) that one drug will perfectly replicate the integrative nature of exercise.

However, with a more complete understanding of how exercise regulates adaptations at the molecular level, we are definitely getting closer to that reality. In terms of chronic disease treatment, this could be paradigm-shifting.

For now, breaking a sweat is still the best option for your health, and you can partly thank your histamine system for that.

Study cited

Van der Stede T, Blancquaert L, Stassen F, et al. Histamine H 1 and H 2 receptors are essential transducers of the integrative exercise training response in humans. Sci Adv. 2021;7(16):eabf2856. doi:10.1126/sciadv.abf2856

Alcohol Disrupts Circadian Clocks in Skeletal Muscle

It is becoming increasingly clear that our circadian rhythms play a fundamental role in health (and disease) and therefore, maintaining “aligned” and robust rhythms is a must. Without going into an in-depth discussion on our body’s circadian system, in nearly every tissue there are genetic “clocks” that control protein translation and the eventual expression of genes related to mood, metabolism, hormones, cognitive function, and physical performance. These genes oscillate throughout the day, peaking and troughing at different times that correspond to when our physiology needs them. It’s a fine-tuned, coordinated act of biology that matches  our internal environment with external conditions.

Unfortunately, several things in our modern environment can throw our circadian rhythms out of line including mistimed light exposure, food intake, and poor sleeping habits. Modernity is a blessing for productivity and 24/7 living, but a curse to our circadian clocks.

One “modern” vice that may also impact circadian rhythms is alcohol consumption. Though many can moderate their alcohol intake, there is no denying that in America and throughout the world, a lot of people just drink too much, and often too much at one time — referred to as binge drinking (exceeding 5 drinks for men and 4 drinks for women in a 2-hour sitting.) The subjective effects of a nighttime bender on sleep and the next day’s productivity are obvious, but could alcohol be causing these effects through its impact on our circadian rhythms?

A study published in the American Journal of Physiology: Endocrinology and Metabolism, investigated the effects of a single binge drinking episode on the expression and pattern of circadian rhythm genes. Specifically, they looked at gene expression in skeletal muscle, a tissue with a major role in metabolism and performance, which may provide insight into the effects of alcohol on several metabolic and/or muscle-related diseases.

Brief study methods

This study was conducted on female mice who were randomly assigned to either a control condition who received a saline injection or a “binge drinking” condition who received an injection of alcohol at a dose of 5g/kilogram of body weight. This dose was justified by the authors as being translatable to human consumption in terms of its effect on blood alcohol concentration (BAC.)

Muscle samples were taken from groups of mice at baseline, 4, 8, 12, 16, and 24 hours post injection. A follow-up experiment extended this sampling to 28, 32, 36, 40, 44, and 48 hours post injection.

The muscle samples then underwent RNA sequencing, cDNA synthesis, real-time PCR, and Western-blot analyses to quantify genes and proteins of interest, which can be seen in the tables below and most of which play an integral role in the core molecular clock in skeletal muscle.


Below is a brief outline of some of the main findings.

  • Binge alcohol consumption disrupted the expression of circadian genes up to 48 hours post injection, including clock, Bmal1, Per1, Per2, Cry1, Cry2. 
  • Alcohol disrupted the expression of clock-controlled genes including Rorɑ, Rev-erbɑ, Myod1, Dbp, Tef, and Bhlhe40
  • The changes in clock genes and clock-controlled genes persisted well beyond the point at which blood alcohol content returned to baseline (~12 hours), indicating that binge drinking had lasting effects
  • Alcohol disrupted (abolished) the oscillation in several circadian and clock-controlled genes from 0-24 and up to 48 hours post injection
  • Skeletal muscle and liver clock-related genes were affected differently by alcohol consumption — indicating unique effects of alcohol on different tissues in the body
  • The alcohol binge increased levels of corticosterone (cortisol) in the mice for up to 8 hours
  • Blocking the increase in corticosterone had little effect on the alcohol-induced reduction in core clock gene expression, suggesting the effects were independent of this hormone

In large quantities, alcohol is not good for the brain or the body. Even in more moderate quantities, alcohol is likely detrimental, but can probably be consumed with minor adverse effects. However, this study provides some very compelling data that acute alcohol intoxication can impact circadian rhythm gene expression and that these effects may last up to 2 days. Though this study was conducted in mice, it nonetheless supports what is known and what many of us may have experienced.

This study is important in telling us not about alcohol’s negative health effects, but the route through which they are mediated. As I mentioned in the introduction, circadian clock genes control the expression of genes responsible for metabolism and skeletal muscle function, among others. The negative effects of alcohol on insulin resistance, glucose tolerance, fat storage, muscle building, and exercise performance are thus likely driven through its effects on the circadian system — a sort of “alcohol-induced jet lag” for lack of a better analogy.

In a majority of real-life scenarios, alcohol consumption is also paired with known circadian disruptors including late-night light exposure, sleep deprivation, and food intake at odd times of the day (nobody needs that 2 a.m. pizza.)

The official word for an environmental cue  that provides time-of-day information to our circadian system is Zeitgeber. Given these results, alcohol can definitely be classified as such and therefore, the amount and timing of alcohol consumption, like that of food, seems to play an integral role in our physiology.

Study cited

Binge alcohol disrupts skeletal muscle core molecular clock independent of glucocorticoids. Abigail L. Tice, Joseph A. Laudato, Michael L. Rossetti, Christopher A. Wolff, Karyn A. Esser, Choogon Lee, Charles H. Lang, Cynthia Vied, Bradley S. Gordon, and Jennifer L. Steine. American Journal of Physiology-Endocrinology and Metabolism 2021 321:5, E606-E620

Nighttime Awakenings Harm Sleep-Deprived Hearts

We’ve all experienced a situation where a particularly good dream or night of deep sleep is interrupted by an alarming noise, urge to go to the bathroom, or sometimes for no apparent reason at all. These nightly awakenings, technically termed “spontaneous nocturnal arousals”, may seem relatively harmless. Most people have a fine time going right back to sleep following a nocturnal arousal, and do so fairly quickly. 

However, the cardiovascular impact of these nighttime arousals may actually be significant from a long-term health perspective. Several things happen when one awakes from sleep, including a brief and transient “spike” in heart rate and blood pressure, which may also be accompanied by an increase in autonomic sympathetic nervous system activity. Since these cardiovascular stimulations are relatively short-lived, they may not pose a substantial risk to health. However, an augmented cardiovascular response to an awakening or a response that takes longer to subside (i.e. return to baseline) could be harmful for the heart and blood vessels.

As important as sleep quality is (sleep quality being also related to nocturnal arousals or awakenings), sleep quantity (how much sleep you get per night) has been more strongly associated with increased cardiovascular disease risk, among others. What is less known is how short sleep duration elevates cardiovascular risk in sleep-deprived individuals. 

As a new study published in the American Journal of Physiology: Heart and Circulatory Physiology suggests, habitual short sleep duration might augment the cardiovascular response to nighttime awakening and therefore, negatively impact acute cardiovascular health and chronic cardiovascular disease risk. This could be one link between a reduced nightly sleep duration and cardiovascular diseases.

Brief study methods

Healthy adult men (20) and women (15) were recruited for this study. For about 11 days on average, all participants had their sleep monitored at home using wrist-worn activity monitors. These data were then used to categorize participants as short sleepers or normal sleepers; receiving <6.93 or >6.93 hours of sleep per night, respectively. This cutoff point for short or normal sleep falls right in line with current sleep recommendations that advocate for adults to receive >7 hours of sleep each night for optimal health.

In addition to baseline habitual sleep characteristics, participants underwent a single overnight laboratory polysomnography sleep assessment which measured brain wave activity (EEG), electrocardiography (ECG), electromyography (EMG), airflow, blood oxygen levels, and limb movements throughout one entire sleep period. 

The primary outcome of this study was the heart rate response to spontaneous arousals — how much did heart rate increase during each awakening and how long did it take for heart rate to return to baseline (heart rate recovery). The heart rate response was then compared between the short sleepers and normal sleepers to determine the impact of habitual sleep duration on this variable.


One “result” to highlight first is that there was no baseline difference in sleep characteristics between the short sleep and normal sleep groups other than their habitual sleep duration. This is important because it allows the findings to be directly related to sleep duration, and not some other variable such as sleep quantity or an uneven distribution of sleep disorders between these groups. 

Given that interlude, let’s take a look at some of the main findings.

  • Heart rate during recovery from nighttime arousals was significantly elevated in the short sleep group vs. the normal sleep group

In the figure below, you can observe that beginning at cardiac cycle number 10 after the arousal onset, heart rate in the short sleep (SS) group was elevated significantly compared to the normal sleep (NS) group until cardiac cycle 24.

  • Contrary to the initial hypothesis of the authors, there were no differences in the heart rate response to arousal between men and women

Interestingly, this finding is a bit in contrast to what some literature has shown — a heightened (i.e. more adverse) cardiovascular response to sleep deprivation among women compared to men. As you can see in the graph below, there were no sex differences in heart rate reactivity to the nighttime arousals in this study.

While it may seem like this is just another study telling us that we should sleep more, I think that the implications are a bit more interesting than that. Clearly it is important to get enough sleep, given the known impact that insufficient sleep can have on daytime metabolic, cognitive, and physical function. These data provide compelling evidence that habitually falling short on sleep can exert negative effects during the night as well.

The night is a time when our body — and in particular our nervous system and cardiovascular system — goes into a restoration mode. Sleep is essential to give these systems a break. If you are routinely missing out on the 7-9 hours recommended for most adults, it seems like you might be putting your cardiovascular and nervous systems at risk by reactivating them during the night. Over time, this could have effects ranging from cardiovascular remodeling to elevated blood pressure and eventually, the development of one of many cardiovascular diseases.

Show your heart some love, and give it at least 7 hours of rest each night and, ideally, at the same time each night. A consistent, regular sleep habit is one of the best things you can do for your cardiovascular health, and the benefits extend well beyond that.

Study cited

Blunted heart rate recovery to spontaneous nocturnal arousals in short-sleeping adults. Jeremy A. Bigalke, Ian M. Greenlund, Jennifer R. Nicevski, Carl A. Smoot, Benjamin Oosterhoff, Neha A. John-Henderson, and Jason R. CarterAmerican Journal of Physiology-Heart and Circulatory Physiology 2021 321:3, H558-H566

Exogenous Ketones For Brain Health and Cognition

This post originally appeared as my weekly newsletter, which you can subscribe to HERE.

The metabolic and cardiovascular harms of obesity are well known, which is alarming given that obesity rates in the US are somewhere around 40%, with similar statistics around the world. 

Obesity also poses a danger to brain health — increasing the risk for cognitive impairment and decline. Why this occurs could be due to several reasons but in part, is proposed to involve reduced blood flow to the brain and lower levels of a molecule known as brain-derived neurotrophic factor (BDNF) — which has been called “Miracle Gro for the brain” because of its effects on the growth and strength of neurons.

Along with reduced blood flow, hyperglycemia (elevated blood glucose) following meals can also impair cognitive function and negatively impact brain health. Obese and diabetic individuals may also suffer from insulin resistance, which reduces glucose availability to the brain and impairs brain metabolism.

While these effects are pronounced in obesity, all of us are concerned with maintaining, or better yet improving, our brain health and cognitive abilities. Supplements for brain performance are pretty scarce (as is the research to support them), however, exogenous ketones are gaining popularity as a supplement with potential neurological benefits.

Our body produces ketones when we are in a “fat-burning” state — which can be leveraged through fasting or a very low-carbohydrate diet. When one is in ketosis, their liver is using fatty acids to produce ketones (beta-hydroxybutyrate or 𝛃-OHB being one) which can then be used by muscles, the heart, and the brain for energy. In particular, the brain seems to readily utilize ketones for energy and does so quite efficiently. This “alternative” energy source might be superfuel for the brain and body.

Ketone metabolism in the brain and body. Source: https://doi.org/10.3390/ijms21228767

Very few studies have looked at how prolonged ketone supplementation may impact brain health and performance. Some acute infusion studies (where 𝛃-OHB is infused at a high dose into the body) suggest beneficial effects, but the impact of elevating ketones via supplementation over weeks to months are not well established.

A new study published in The Journal of Physiology investigated the impact of a 14-day ketone supplementation period on markers of brain blood flow and cognitive performance in a group of otherwise healthy adults with obesity.

Brief study methods

This was a randomized, placebo-controlled, crossover, counter-balanced study — meaning that all participants completed both the experimental and placebo conditions, did so in a random order, and neither the investigators nor the participants were aware of which condition they were in until the end of the study.

Two different experimental conditions were completed, each lasting 14 days:

Ketone supplement condition: participants consumed a ketone supplement three times per day (once before breakfast, lunch and dinner) for 14 days.

Placebo condition: participants consumed a placebo supplement three times per day for 14-days as in the ketone supplement condition.

Diets were controlled — all of the food consumed by participants during the study was provided by the researchers (major strength) and contained approximately 50% carbohydrate, 30% fat, and 20% protein.

Cerebral blood flow (CBF) was measured using ultrasound in the common carotid (CCA), vertebral (VA), and internal carotid (ICA) arteries. Cognitive performance was measured using three tests: the digital symbol substitution task (DSST), the Stroop test, and the task-switching test (TST). These have all been shown to reliably measure aspects of cognition including working memory, processing speed, selective attention, and inhibitory control. BDNF was measured in serum and plasma.

All measures were taken pre- and post-intervention.


  • Cognitive performance: performance on the DSST significantly improved after the ketone supplementation condition, but no differences were observed during the Stroop test or TST.
  • Blood flow: flow in the common carotid (CCA) and vertebral (VA) arteries was elevated after the ketone supplementation condition
  • Vascular conductance (CVC) and shear rate increased in the vertebral artery (VA) following ketone supplementation
  • Blood flow increases in the common carotid (CCA) and vertebral (VA) arteries was correlated with improvement on the DSST
  • No changes were observed in BDNF in either the ketone or placebo condition

As far as I know, this is the first study to look at the cognitive effects of supplementing with exogenous ketones, at least in a population that is more or less healthy. By this I mean that, although they were categorized as obese, none of the participants had any indications of cognitive impairment nor did they have any other comorbidities or for that matter, even elevated blood glucose.

For this reason, I’d consider generalizing these findings to “healthy adults” in terms of how ketones might impact brain function. This is quite promising. The keto diet and fasting are both purported to help with mental clarity, performance, focus, etc. Exogenous ketones are more appealing, in my opinion, because they can be used as a nootropic (cognition-enhancing supplement) without requiring much lifestyle modification. It is one thing to improve cognitive function in someone with low levels at baseline, and another (exciting) thing to enhance cognition in normally-functioning individuals.

The results of this study suggest that the improvements in cognitive performance were caused in part by elevated blood flow to the brain. The same group conducting this study has published that exogenous ketone supplementation also improves peripheral endothelial function (brachial artery flow-mediated dilation) in the same group of participants. Add cardiovascular benefits to the cognitive benefits of exogenous ketones and you start to build a pretty compelling case for regular (i.e. daily) supplementation with ketones.

Right now, this may not be feasible due to the somewhat cost-prohibitive nature of exogenous ketones (around $8 for a serving right now for the cheapest commercially-available product). However, companies are developing more cost-effective alternatives. For what it’s worth, the supplement used in this study was the BHB monoester sold by H.V.M.N. (a company to which I have no financial ties).

If you are interested in experiencing the effects of these novel supplements, I would suggest trying one of the few ketone esters available right now. Disclosure: I have no investments in any of these companies, but do freelance work for Juvenescence as a content writer.

Juvenescence: Metabolic Switch ketone ester

H.V.M.N.: ΔG Ketone monoester

KetoneAid: Ketone monoester

As always, thanks for reading.

Studies cited

Walsh JJ, Caldwell HG, Neudorf H, Ainslie PN, Little JP. Short‐term ketone monoester supplementation improves cerebral blood flow and cognition in obesity: A randomized cross‐over trial. J Physiol. Published online October 4, 2021:JP281988.

Walsh JJ, Neudorf H, Little JP. 14-day ketone supplementation lowers glucose and improves vascular function in obesity: a randomized crossover trial. The Journal of Clinical Endocrinology & Metabolism. 2021;106(4):e1738-e1754.

Supplementing with Nitrates to Enhance High-Intensity Exercise Performance

The world of sports supplements (really supplements in general) is riddled with imposters, plagued by unverifiable claims, and lacking in regulation. For this reason, there are generally a lot of supplements available, but only a few that really show any efficacy in doing what they claim to do or containing what they claim to contain. For those who may be curious, the supplements with the most evidence to support their use include caffeine, creatine, beta-alanine, and sodium bicarbonate.

I’ll add another to that list — nitrates and nitrites. These aren’t really “supplements” — they’re found in leafy greens and beets, among other sources. However, nitrate/nitrite-containing products like concentrated beetroot juice and beet juice “shots” are available for anyone to buy and ingest and have been used in many research studies for their potential health and performance-enhancing effects.

The effects of nitrates/nitrites on cardiovascular health and performance are large and well-evidenced. This is because nitrates/nitrites, once ingested, get metabolized into a molecule called nitric oxide (NO). NO has many beneficial effects including promoting blood vessel relaxation and increasing blood flow delivery to our muscles. This is why research on “supplements” that boost NO is so popular. This in addition to the fact that nitrates/nitrites are cheap and easy to consume in this form or by eating vegetables which contain them.

For exercise and sports performance, nitrates/nitrites could provide a real benefit to recreational and high-level athletes. As a “risk-free” dietary supplement, it is worthwhile to understand the effects that ingesting nitrates/nitrites could have for physical performance, most of which are hypothesized to come from enhancing oxygen delivery to working muscles.

Mechanism of nitric oxide in vascular smooth muscle: https://www.nejm.org/doi/full/10.1056/NEJMra051884 

A recently published study that appeared in the journal Current Research in Physiology investigated whether a supplement containing nitrates/nitrites from beets could enhance high-intensity exercise performance, which could provide some rationale for using NO-boosting supplements as a “pre workout” or as a daily ergogenic supplement.

Brief study methods

This study was conducted in trained male cyclists. In a double-blind crossover study, participants completed two interventions in which they received either a placebo or a nitric oxide-enhancing (NOE) supplement.

Supplement used: Humann Beet Elite

At the start of each trial period, participants consumed the placebo or NOE supplement for 2 days and then underwent a lactate threshold test. They then supplemented for 3 more days before undergoing a high-intensity interval training (HIIT) session.

The researchers were interested in outcomes including power output (Watts) at lactate threshold and the total time to exhaustion, work output, energy expenditure, distance traveled, and intervals completed during the HIIT session at the end of the supplementation week. Levels of muscle oxygenation and hemoglobin saturation were also measured during exercise.


  • The NOE supplement increased lactate threshold power by 17.2% vs. the placebo
  • The NOE supplement increased HIIT performance by improving time to exhaustion, number of intervals completed, distance traveled, and total energy expended
  • The NOE supplement increased muscle oxygenation and hemoglobin saturation during HIIT work and rest intervals compared to the placebo

I’m a bit surprised that the NOE supplement was able to increase performance in already well-trained, highly fit athletes. A lot of the nitrate/nitrite supplement literature is conducted in clinical populations such as those with arterial disease, heart failure, or other cardiovascular complication in which blood flow and oxygen delivery may be impaired. In such cases, elevating levels of NO would improve exercise tolerance and performance by enhancing oxygen delivery. The fact that such a supplement also increases performance and muscle oxygenation in trained athletes (who we might assume have adequate levels of NO) is promising while also a bit unexpected.

There are several reasons to begin supplementing with nitrates/nitrites including the well-known cardiovascular health benefits and the fact that you might also be able to increase your performance in the gym or at your local road race. It’s an extremely low-risk supplement. Whether using the product in this study, one of the many other beet-containing products available, or through daily consumption of leafy green vegetables and beets, getting your nitrates/nitrites can help your heart and your 5k PR to flourish.

Exercise before Fasting Kick-starts Ketosis

This post originally appeared as my weekly newsletter, which you can sign up for HERE.

Fasting for weight loss is extremely popular. However, there are many other benefits of fasting that are independent of losing fat, including the proposed effects on healthspan and lifespan. While a lot of data have been gathered in animal models, there is good evidence that fasting activates several “pro-longevity” pathways in the body which make our cells more resilient, clear out damaged proteins, and improve overall metabolic health. 

Many benefits of fasting may also be related to the production of ketones during fasting. Ketones are formed by our liver when the body is in a fat-burning state and insulin is low, and can be used by our brain and other tissues as an “alternative” energy source. Ketones have also been shown to act as signaling molecules, activating similar pathways as fasting. For this reason, there is a growing literature on using the ketogenic diet, fasting, and exogenous ketones (all of which elevate levels of blood ketones) to leverage the metabolic and (potential) lifespan-enhancing benefits.

Fasting is a great way to elevate blood ketones, as is a ketogenic diet. However, exercise is also a potent activator of ketosis and perhaps better and more effective than fasting. This is because exercise rapidly depletes liver glycogen and therefore, “switches” the body to a fat-burning state which continues into the post-exercise window — something known as “post-exercise ketosis.”

The question then becomes whether stacking interventions could be a more effective way to promote and sustain ketosis?

A new study published in the journal Medicine and Science in Sports and Exercise (MSSE) was interested in this question. Specifically, the goal of this study was to determine how a 36-hour fast influences the production of beta-hydroxybutyrate (BHB, which is categorized as a ketone) and how performing intense exercise at the beginning of this fast would influence ketone production.

Brief study methods

20 young individuals took part in this study (11 men and 9 women with an average age of 26.) In a randomized order, participants complete two different arms of the study:

– Fasting only intervention: 36-hour water-only fast

– Fasting + exercise intervention: 36-hour water-only fast with a bout of high-intensity treadmill exercise at the beginning of the fast

It is worth noting the type of exercise performed in this study, which was intense treadmill running at 70% of participant’s heart rate reserve until they had burned about ~600 calories — the amount contained in the pre-fast standardized meal provided to all participants. The exercise was designed to burn glucose/glycogen as the primary fuel source.

At the start of the fast (hour 0), 12, 24, and 36 hours, levels of blood BHB, insulin, and glucagon were measured, as were psychological measures such as hunger, thirst, stomach discomfort, and mood.


– The exercise + fasting condition resulted in a larger area-under-the-curve (AUC) for BHB — indicating a greater total exposure to elevated ketones throughout the fast

– The exercise + fasting condition expedited the time taken to achieve ketosis by ~3.5 hours (participants entered ketosis quicker when exercising before the fast)

– No differences in insulin AUC were observed between conditions, but exercise + fasting resulted in a larger glucagon AUC

– Hunger, thirst, and stomach discomfort were similar for both conditions

– Participants reported feeling more “depressed” during the non-exercise condition vs. the exercise + fasting condition

The first thing to note about these findings is the general observation of how long into a fast it takes to achieve clinical levels of ketosis — which are defined as levels of BHB >0.5 millimolar (mM.) In this study, on average, it took participants ~21 hours to reach this threshold. For those interested in how fasting affects ketones, this data is useful because it informs how long one might need to fast to boost blood ketones to this level or above. Granted, one’s usual diet and physical activity, as well as many other factors, will drastically influence the magnitude and timing of ketone production in the body.

In the exercise condition, it took only ~17.5 hours to reach a BHB level of 0.5mM, and BHB levels were 43% greater throughout the entire fast compared to a fast without exercise. If you want to put your body into ketosis quicker, it seems like exercising before you start your fast is the way to do it. Furthermore, it doesn’t seem like exercise elevates hunger levels or mood any more than a 36-hour fast with no exercise and may reduce your “depressive” symptoms during the fast (thanks, endorphins!)

There are many ways to build upon this study and several questions that remain. For instance, how does exercise placed at different time points during a fast affect ketone levels? Would the results be the same if one exercised midway through the fast or rather, ended a 36-hour fast with a bout of exercise?

Many protocols can work for achieving ketosis and trying to enhance the metabolic adaptations of fasting and exercise. My routine typically lends itself to ending my fast (or rather my bout of time-restricted feeding) with exercise. This will usually be about 10-12 hours after my last meal (dinner). Then, I’ll continue to fast for about 2-3 hours before eating breakfast/lunch. While I’m not sure what my levels of ketones are during this protocol, measuring is something I’ve considered and may do in the near future as an n=1 experiment.

Thanks for reading.

Don’t Blame Aging for a ‘Slowed Metabolism’

This post originally appeared as my weekly newsletter, which you can sign up for HERE.

It is commonly stated and generally well-accepted that metabolism declines with age. As one leaves their early 20s and 30s and enters middle-age, the body “slows down,” — burning less calories than it once did. Coincidentally, weight and fat mass start to creep up as one progresses throughout life, and the slowing down of metabolism is typically to blame.

New data suggest that many of our prior conceptions about metabolism and aging may be wrong. In this study, researchers analyzed a database of diverse individuals (individuals from many countries) from which they gathered data on total daily energy expenditure (TEE) to determine the trajectory of metabolism throughout the life course of a human. How does metabolism compare at birth (or very shortly after) to when you’re in your early to late 90s?

Study: Daily energy expenditure through the human life course

The findings were (perhaps) quite surprising. The paper describes four distinct “phases” of metabolism that seem to emerge throughout life. As neonates (birth to 1 year of age), our metabolism is higher than any other point in life (after adjusting for body mass, of course) — almost 50% higher than adult levels. This makes sense, as this is a period of rapid growth and development. Metabolism begins to decline thereafter until about age 20 — the “juvenile phase.” The decline in total energy expenditure of about 2.8% per year continues until about age 20.5, after which it reaches a plateau.

Adulthood, age 20 – 60, is a period where total energy expenditure is stable, along with fat-free mass, up until age 63. Finally, after age 63, a period known as older adulthood, we see a drop in energy expenditure consistent with a drop in fat-free mass. For context, in someone who is 90 years old, energy expenditure is around 26% lower than that of a middle-aged adult.

What do these findings mean? Well, for one, they tell us that a “slowed metabolism” may NOT be the reason for the mid-life weight gain and other health problems. In fact, this study did not find any evidence that weight or fat mass increased between the ages of 20 and 60, nor were there seemingly any differences between men and women.

As to what causes these declines in energy expenditure, two likely candidates exist — reductions in physical activity/exercise throughout life and reduced tissue metabolism (our organs use less energy with age.) Both situations are likely true and the good news (and perhaps bad news) is that one of these is largely under our control. To “fight” the age-related decline in energy expenditure, you can be aware of your activity levels and maintain or even increase them with age — this will also help stave off age-related losses in muscle mass.

This may also explain why as adults, and especially as older adults, people tend to eat less. Perhaps the body is fine-tuned to recognize reductions in energy need, and responds accordingly by reducing appetite. This may also be why those who fail to rein in their appetite with age do seem to experience an age-related increase in weight and fat.

I hope you found this discussion interesting. See you next Friday!

Cognitive Deficits from COVID, “4-second” Workouts, and How Childhood Stress Impacts CVD Risk

This week’s post (which originally appeared in my weekly newsletter) includes studies that are hot off the press and cover topics including the effects of childhood adverse experiences on future cardiovascular health, the long-term effects of COVID-19 on cognitive performance, and a 4-second workout that has potent effects on fitness and anaerobic performance.

Study #1: Childhood psychosocial stress is linked with impaired vascular endothelial function, lower SIRT1, and oxidative stress in young adulthood

We often single out dietary or lifestyle factors when talking about one’s risk for developing cardiovascular disease (CVD), but mental & emotional stress may also be major factors to consider when we think about health throughout one’s lifespan. In this regard, research has shown that exposure to adverse childhood experiences — also known as ACEs (including emotional/physical/sexual abuse, violence, and neglect) — are associated with disease risk in adulthood.

This study investigated whether exposure to ACEs is associated with impaired endothelial function during adulthood. Given that endothelial dysfunction is a major step in the development of atherosclerosis and CVD, findings could potentially uncover a mechanism linking ACEs to CVD.

Two groups of women (average age ~21 years) were studied: one group who had been exposed to ACEs during childhood and another group who had no previous ACE exposure. Vascular function, levels of a gene related to longevity and CVD risk known as SIRT1, and oxidative stress were compared between groups. In addition to baseline comparisons among groups, researchers investigated whether an 8-week exercise training program would enhance vascular function in women who had experienced ACEs.

Results: Endothelial function was lower in the women with exposure to ACEs, as were levels of SIRT1 — which could mean that these low SIRT1 levels are somehow causing the endothelial dysfunction seen in this group. Levels of oxidative stress were not different between the ACE and no ACE groups.

Surprisingly, 8 weeks of aerobic and resistance exercise training did not increase vascular function in the ACE group. Overall, the results of this study point to a potential mechanism (reduced endothelial function and SIRT1 levels) by which ACEs contribute to a greater CVD risk in adulthood.

Study #2: Cognitive deficits in people who have recovered from COVID-19

There is no shortage of studies on COVID-19 and, as of recently, studies are emerging on “long COVID” — a generally uncharacterized condition in which individuals previously infected with COVID-19 experience symptoms including cardiovascular complications, brain fog, and fatigue. This is a relevant area of study, because while we know the acute impact of COVID on the lungs, the long-term implications of the disease may be even more of a burden on both individuals and the healthcare system. Whether the ravages of infection persist long after the disease has been “shed” is a relevant problem to investigate.

Results of a very large cross-sectional study (81,337 participants) provide some convincing evidence that COVID-19 may have lasting consequences for cognition and brain health, among the other maladies it inflicts upon its victims.

Results: Analyzing a dataset from participants who completed an online cognitive performance test that included items related to COVID-19 infection, authors found that compared to individuals who had never been infected with COVID-19, previously infected individuals “exhibited significant cognitive deficits.” These deficits were more pronounced among those who had been hospitalized with the disease and/or those with “biological confirmation” of infection. In fact, as the figure shows, the degree of cognitive deficit was essentially graded with the severity of disease.

There are a few limitations to a study like this — first and foremost that there are no “pre-infection” cognitive performance data; meaning we cannot compare what an individual scored on the test before infection to what they scored on the test after infection. However, given that there were seemingly no baseline differences in cognition among infected vs. never infected individuals, the data support some causal role of COVID-19 infection on cognitive performance.

We can now add cognitive and neurological effects to the somewhat established cardiovascular effects that make up “long COVID.” While we are still fighting COVID-19 and trying to prevent its spread, it seems as if we must be just as diligent in developing strategies (diet, exercise) to help infected individuals recover from and surmount the chronic effects of this respiratory disease.

Study #3: Four-Second Power Cycling Training Increases Maximal Anaerobic Power, Peak Oxygen Consumption, and Total Blood Volume

If you’re looking for the shortest workout possible (literally) that provides the most bang for your buck, then look no further.

High-intensity interval training (HIIT) has been improved upon in recent years, with many labs looking to decrease the time spent doing activity to as little as possible. This comes with a “price”, however, for to get the same benefits, one must exert exponentially more effort during these curtailed exercise bouts. A question that continues to be unresolved is: “what is the LEAST amount of exercise one can do while still receiving the MOST benefit?”

This study took that question to a new level — testing whether an extremely short “power cycling” regimen could enhance maximal aerobic capacity, blood volume, and anaerobic power.

These sessions were SHORT. For 8 weeks, participants completed 3 sessions per week. Each session involved 30 sprints that lasted 4 seconds each! Between each “all-out” effort was a rest period that began at 30s in the early weeks and then dropped to 24 and eventually 15 seconds of rest. If you do the math, that results in a total training time per session of 17 minutes at the beginning and only 10 minutes at the end of the intervention. 10 minutes per session — literally 30 minutes per week of exercise.

Results: After 8 weeks, participants had increased their VO2 peak by ~13% and their anaerobic power by around 200 Watts. Their blood volume, which is also associated with endurance adaptations and performance, also increased.

If we talk about a “minimal effective dose” for exercise — this might be close to the limit. There have been similar studies looking at 10-second “all-out” sprints, with a similar session length, but as far as the length of actual efforts is concerned, 4 is the shortest the literature has seen.

I hate to say it, but studies like this leave us with no excuse not to work out. In as little as 30 minutes per week of, admittedly, hard effort, one can improve cardiorespiratory fitness and probably several other cardiovascular and metabolic biomarkers not looked at in this study.

That’s all for this post. I hope you found at least one of these studies interesting and took away some practical, useful information. Thanks for reading.

Morning Light Boosts Mood, Post-meal Sitting Worsens Blood Vessel Function, and Heat Therapy for Vascular Health

In this weeks post, we will be reviewing three recent studies that delve into the effects of morning light exposure on mood and behavior, whether the glycemic index of a food influences the impact of prolonged sitting on blood vessel function, and how passive heat therapy might be a useful tool to combat blood vessel dysfunction and cardiovascular disease.

This post originally went out as an installment of my weekly email newsletter. If you would like to subscribe to my newsletter, you can do so HERE.

Study #1: Light affects behavioral despair involving the clock gene Period 1

Our mood is heavily influenced by our environment. Light (from the sun) is a well-known regulator of mood and behavior in humans and animals. Our brain needs to receive light-dark cues in order to properly entrain our circadian rhythms to our environment, which allows a precise coupling of internal physiological processes with external events. An example of when this goes awry is seasonal affective disorder (properly acronymed SAD), a depressive-like state that emerges during long winter months and at northern latitudes, when sun exposure is extremely low. This illustrates the profound mood-boosting and cognition-enhancing effects that properly timed light exposure can have on health, and the adverse effects that can be wrought from a lack of exposure.

This study used a 30-minute period of morning light exposure (a “light pulse”) in mice (technically night light exposure, since mice are nocturnal) to demonstrate that light activates a specific circadian clock gene within the brain known as Period 1. Following the light exposure, mice demonstrated reduced despair behaviors, indicating that light may be beneficial for regulating mood and even depressive-like symptoms. Mice who had their Period 1 gene knocked out did not experience any beneficial effects of light exposure, implicating this clock gene in the beneficial effects of light on mood and behavior.

Application: Expose yourself to light first thing in the morning! This is known to have positive effects on mood, setting your circadian rhythm, and just helping you wake up! There is also some evidence that you should expose yourself (really your eyes) to light at different times throughout the day in order to keep providing your body with light and time cues. A morning, early-afternoon, and evening walk could be one of the best ways to leverage this biohack. Couple light exposure with some exercise and food for a more robust circadian effect.

Study #2: Arterial stiffness responses to prolonged sitting combined with a high-glycemic-index meal: a double-blind, randomized crossover trial

Sitting is not the new smoking, as you may have read in some (misleading) news headlines. However, there is no doubt that too much sitting is probably not the best for health, since a high amount of sedentary behavior is associated with a wide range of metabolic and other diseases. Sit as little as you can, but don’t stress if your day job requires it. You can probably counteract sitting by engaging in moderate to high levels of physical activity and taking frequent walk breaks throughout the day.

Our cardiovascular system may be uniquely susceptible to the detrimental effects of sitting. Being immobile for a long period of time reduces blood flow throughout our body, which can cause vascular dysfunction in the legs, arms, and the brain and increase the stiffness of our arteries. Over time, this could expose one to a greater risk for cardiovascular complications. One thing that many people do while sitting is eat. For this reason, it would be beneficial to understand how prolonged sitting combined with a meal (particularly one that is high in sugar or simple carbohydrates, which are also known to be detrimental to vascular health) may influence blood vessel function.

This study investigated the combined effects of prolonged sitting and a high-glycemic-index (GI) meal on total body arterial stiffness. Young healthy adults were exposed to a 3-hour bout of sitting after consuming either a high- or a low-GI meal. The GI of a food refers to how a it affects blood sugar — with a high GI meal causing a more rapid and elevated blood glucose response. As you can see below in figure 2 from the study, the high-GI meal spiked blood sugar much more than the low-GI meal and was elevated throughout the sitting period until around 2 hours, when it dropped below the low-GI meal (sugar crash, anyone?)

Arterial stiffness was significantly increased after the prolonged sitting bout, however, the high- and low-GI meal had a similar response — meaning the high-GI meal was not any more detrimental than the low-GI meal to arterial stiffness.

Application: While this study was in young, healthy males and females, it indicates that eating a meal and sitting for a period of 3 hours is probably not great for our blood vessels. It doesn’t seem like the type of meal matters much in this case, since no differences were found between the high and low-GI meals. The takeaway here would be to never sit for more than 3 hours at a time (I would recommend no more than 30 minutes to 1 hour at a time), especially right after a meal. I’m a strong advocate for a post-meal walk of 15-20 minutes before I return to sedentary work, finding that this helps with my digestion, cognition, and overall energy levels.

Study #3: Improvements in vascular function in response to lower limb heating in young healthy males and females

Heat exposure (sauna, exercise in the heat, hot baths) is a great way to improve bodily health. There is an abundant literature on the effects of short-term and regular sauna use on cardiovascular health, with many of the effects “mimicking” those observed with exercise training — including reduced blood pressure, improved resting HR, and better vascular function and reduced arterial stiffness.

This begs the question of whether we can develop easy-to-implement strategies to improve vascular health and function in individuals who may be at risk for conditions like peripheral artery disease (PAD) and hypertension. Not everyone has access to a sauna, and lower-cost heat therapies might be a more feasible and easy way for individuals to access regular heat exposure.

This study investigated whether lower-limb heating could acutely improve markers of arm and leg vascular function and arterial stiffness in healthy young men and women.

Participants took part in two different heating conditions: one involving 45 minutes of ankle-level hot water immersion and another involving 45 minutes of knee-level hot water immersion. The temperature of the water was 45C, or 113F, which would be similar to a pretty warm hot tub. 

In both heating conditions, arm vascular function was improved and leg arterial stiffness was reduced. Interestingly though, leg vascular function was not improved after heating, even though the legs were the limb being exposed to the hot water immersion. What this tells us is that the heat therapy is having system-wide benefits that are likely due to the release of certain inflammatory molecules. Indeed, it was also shown that a signaling molecule known as heat-shock protein (HSP) was elevated after knee-level hot water immersion. HSPs likely play a major beneficial role in the adaptations to any heat therapy, and also are implicated in the benefits of exercise.

Application: If you’re lucky enough to have access to a sauna, use it, OFTEN! If not, it seems like less intensive forms of heat therapy may also have cardiovascular benefits. Submerging yourself in a hot bath (though it likely won’t be nearly as hot as the water in this study), sitting in a hot tub, or using local heating such as in this study can all be effective forms of “thermal therapy.” If anything, a hot bath can help you unwind and destress, which has benefits for your physical and emotional health as well.

I hope you learned something interesting from at least one of these studies, and perhaps found something that you can take away and apply to your own life. See you next week!