Heart Rate Variability: A Valuable Biomarker with A Major Impact on Physiological and Psychological Health

Jesse Oswald • March 13, 2024

Key Points

  • Heart rate variability is a noninvasive, easy-to-measure, and reliable physiological and psychological health biomarker.
  • Heart rate variability can be a great tool to monitor exercise performance and progress as well as the prognosis of various clinical conditions, such as cardiovascular disease and depression.
  • HRV isn’t just one metric; it actually comprises different sub-metrics, with each one generally representing a different physiological system (e.g. metabolism, neurological activation, etc.)
  • The Mediterranean diet, frequent exercise as well as certain lifestyle habits are the most effective ways of improving HRV. 

 

Heart rate is the number of heartbeats per minute, and heart rate variability (HRV) quantifies the heart rate variability. Although the heart rate may be reasonably stable, the time between two successive heart contractions (R-R intervals) can vary considerably at rest; hence, HRV is the beat-to-beat variation in the time intervals between adjacent or consecutive heartbeats, called the inter-beat intervals (IBIs). The oscillations of a healthy heart are complex and constantly changing, which allows the cardiovascular system to adjust rapidly to sudden physical and psychological challenges to homeostasis.

HRV is considered a noninvasive, practical, and reproducible biomarker of autonomic nervous system function since the oscillations between consecutive heartbeats mainly result from the dynamic interaction between the parasympathetic (PNS) and sympathetic nervous system (SNS) inputs to the heart. Specifically, increased sympathetic input decreases HRV, whereas increased parasympathetic input increases HRV. While the SNS activity increases during stress, physical threat, or exercise, the PNS relaxes your body after periods of stress or danger and makes you feel safe and relaxed. The PNS and SNS constitute branches of the autonomic nervous system, which, along with the somatic nervous system, comprise the peripheral nervous system.

 

In a healthy human heart, there is a dynamic relationship between the PNS and SNS. PNS activity predominates at rest, resulting in an average heart rate of ~ 75 beats per minute.

HRV represents the heart's ability to respond to physiological and environmental stimuli. Therefore, the ability of the autonomic nervous system to respond dynamically to environmental changes results in increased HRV and generally indicates a healthy heart. Conversely, a low HRV is associated with impaired regulatory and homeostatic autonomic nervous system functions, which reduce the body’s ability to cope with internal and external stressors.

Many physical conditions and lifestyle habits can affect HRV, including physiological factors (e.g., breathing, circadian rhythms, and posture), non-modifiable factors (e.g., age, sex, and genetic factors), modifiable lifestyle factors (e.g., physical activity, body mass index, smoking, drinking, and stress), and other factors (e.g., medication such as anticholinergics, stimulants, and beta-blockers)

Altogether, a high level of HRV is associated with overall health, self-regulatory capacity, adaptability, and physiological and psychological resilience.

HRV Metrics

HRV can be analyzed via a) time-domain measures, b) frequency-domain measures, and c) non-linear measures.

Time-domain indices of HRV quantify the variability in measurements of the inter-beat interval (IBI), which, as previously mentioned, is the time between successive heartbeats. The two most common measures are the standard deviation of R-R intervals (SDRR), a measure of overall variability, and the root mean square of successive differences of R-R intervals (RMSSD), a measure of beat-to-beat variability.


While time-domain measurements display a parameter versus time, frequency-domain measurements display a parameter versus frequency. A given measure can be converted between the time and frequency domains with a pair of mathematical operators called transforms. Frequency-domain indices estimate the absolute or relative power distribution into four frequency bands or rhythms that operate within different frequency ranges. Therefore, heart rate oscillations are divided into ultra-low-frequency (ULF), very-low-frequency (VLF), low-frequency (LF), and high-frequency (HF) bands.


  • The ULF band (≤0.003Hz) requires a recording period of at least 24 hours. It reflects circadian oscillations, body temperature, metabolism, and activity of the renin-angiotensin system.
  • The VLF band (0.0033-0.04Hz) requires a recording period of at least 5 minutes but may be best monitored over 24 hours. It represents long-term regulation mechanisms, thermoregulation, and hormonal mechanisms.
  • The LF band (0.04-0.15Hz) is typically recorded over a minimum two-minute period and comprises rhythms with periods between 7 and 25 seconds. It reflects a combination of sympathetic and parasympathetic influences.
  • The HF band (0.15-0.40Hz) is conventionally recorded over 1 minute and reflects parasympathetic activity. It is also called the respiratory band because it corresponds to the heart rate variations related to the respiratory cycle (heart rate increases during inhalation and decreases during exhalation).

Different respiratory rhythms affect different frequency bands. Particularly, the LF band is affected by breathing from ~ 3-9 breaths per minute, whereas the HF band is influenced by breathing from ~ 9-25 breaths per minute.



Lastly, the LF to HF power (LF/HF ratio) reflects the balance between the SNS and PNS activity under controlled conditions. A low LF/HF ratio reflects parasympathetic dominance. In contrast, a high LF/HF ratio indicates sympathetic dominance, which occurs when we engage in fight-or-flight behaviours. In addition to time and frequency domain HRV, there are other HRV measures based on non-linear dynamics, such as power-law analysis, approximate entropy (ApEn), dimensionality, and detrended fluctuation analysis (DFA).

 The Effect of Exercise Training on HRV

Exercise training has increased HRV in healthy individuals, with exercise intensity being the strongest determinant of HRV.

The limited body of evidence suggests that prolonged exercise duration can decrease HRV during exercise.


As for the exercise mode, during moderate steady-state exercise, upper body exercise elicits greater HRV compared to lower body and body weight exercise at the same submaximal heart rate and the same absolute/relative % VO2 max work rates.


More importantly, regular physical activity reduces the risk of morbidity and mortality from various clinical conditions, including cardiovascular disease (CVD) and diabetes.


It is strongly recommended for CVD patients, including those who have experienced a myocardial infarction (MI) and patients with chronic heart failure (CHF).


Several studies have documented improvements in HRV via participation in exercise training programs among MI patients.

One study found that following an eight-week cardiac rehabilitation program, participants significantly increased HRV parameters compared to those not participating in the training program.


In another study, researchers reported a 30% reduction in LF/HF ratio after MI patients completed an eight-week endurance rehabilitation program. These improvements continued for one year following participation in the program.

Improvements in HRV may also be achieved through unsupervised low intensity walking programs and anaerobic threshold exercise training.


Physical activity has also been found to benefit HRV in patients with CHF. CHF is characterized by impaired cardiac function and is associated with reduced exercise tolerance and HRV. Improvements in HRV among CHF patients have been observed in supervised aerobic exercise programs, supervised resistance training programs, and home-based training programs.



Nevertheless, the exact mechanisms underlying the beneficial modification of HRV by exercise training in these conditions are unknown. One hypothesis suggests that physical exercise increases cardiac parasympathetic tone and reduces sympathetic cardiac influences. However, more research is required to substantiate these claims. Further research is also needed to identify the exercise regimen, in terms of intensity and duration, that produces optimal improvements in HRV.

HRV as a Tool for Optimization of Exercise Training

HRV, apart from being a tool for assessing autonomic nervous system function, has also been investigated for monitoring training load, individual adaptations to training regimens, and recovery, as well as the early detection of overtraining phenomena.


HRV-guided training elicits greater improvements in maximal training load (+6-8%). Also, it allows significant performance improvements with a lower training load, not only in trained athletes but in untrained individuals. HRV should be measured regularly throughout the year in competitive sports to control the athlete’s response to different training stimuli. Yet, when training adaptations are monitored via HRV, it is necessary to consider the athlete’s training phase. Therefore, more frequent HRV measurements are recommended in the transition and competitive phases, whereas a few weekly ones may be sufficient during the preparatory phase.


What about recovery, though? A subtle balance between exercise stress and recovery is necessary to elicit optimal adaptations and performance improvements. High-performance athletes are constantly exposed to intensive training stimuli in a way that training-induced fatigue, and insufficient recovery may occur. If training is continued without recovery, there is a high possibility of developing overtraining syndrome, which requires several weeks or even months for an athlete to overcome and successfully return to their training.



Since chronic training overload decreases HRV, the use of HRV measurements offers great potential for the early detection and prevention of overtraining.

HRV and Cognitive Function

Participants with high HF-HRV perform better in cognitive tasks than participants with low HF-HRV. More specifically, high HF-HRV was associated with better verbal reasoning ability. In contrast, low HF-HRV had weaker performance in global cognitive functions, such as verbal reasoning abilities, memory responses, and executive functions.



Some studies have also reported a link between low HF-HRV and the risk of developing cognitive impairment, such as Alzheimer’s disease. Moreover, lower LF-HRV is linked to worse cognitive performance, particularly memory, language, and global cognitive scores. Overall, HRV appears to correlate with verbal but not visual cognitive facets. 

Diet and Its Implication With HRV and Mental Health

Various aspects of diet have been associated with HRV. For example, dietary consumption of fatty fish and omega-3 fatty acids is independently associated with HRV. Specifically, greater consumption of tuna or other boiled or baked fatty fish such as salmon and mackerel was associated with improved HRV indices, thus a lower risk of arrhythmic outcomes, including sudden death, arrhythmic coronary heart disease (CHD), and atrial fibrillation.


Furthermore, a Mediterranean dietary pattern, sufficient vitamin and mineral intake, and caffeine consumption have all been associated with increased HRV.


On the other hand, aspects of an unhealthy dietary pattern, such as a high-saturated or trans-fat diet, reduce HRV.

Lastly, although smoking cigarettes and drinking alcohol have negatively been associated with HRV, wine intake, in particular, is positively and independently associated with HRV.


Therefore, the consistent relationship between HRV and diet supports the view that HRV may act as a biomarker of the influence of food and diet on health.


Even though it is clear that diet influences HRV, the pathways underlying such effects are multifactorial and rather complex. It is plausible that the impact of diet on HRV operates indirectly through changes in mental health.


Traditionally, heart rate has been considered a product of emotional response or stress.


Furthermore, many studies have found an association between mental health and HRV. Thus, demanding situations may give rise to an increase or a decrease in HRV. The former might arise when an individual successfully self-regulates the demands of the situation, and the latter may occur when the situation is perceived as threatening. On the other hand, diet influences brain functioning, cognition, and mood, which are then reflected in changes in HRV. 


Notably, the link between HRV and eating disorders points toward the possibility of mutual causation. Most studies investigating HRV in those with anorexia nervosa have found parasympathetic dominance.



Similarly, those with bulimia nervosa are characterized by higher parasympathetic activity, particularly HF-HRV. Another study found reduced HRV in those with a propensity towards disinhibited eating, which is a tendency to overeat in the presence of palatable foods or other disinhibiting stimuli, such as emotional stress. Lastly, a low resting HRV has been associated with adopting maladaptive emotion regulation strategies and poor impulse control problems in identifying emotions.

 

Altogether, it appears that individuals who have difficulty regulating their emotions and are generally depressed are predisposed to adopting emotion regulation strategies such as the consumption of ‘’comfort’’ foods, with a resulting decrease in the quality of their diet. In turn, a poor-quality diet could further exacerbate the reduction in HRV. These data suggest that dietary behaviour and diet quality at least partially mediate the association between depressed mood and HRV. Nevertheless, future research will guarantee more solid evidence on the metabolic pathways linking mood, diet, and HRV. A wide range of diseases is associated with decreased HRV, including CVD, diabetes, obesity, and psychiatric disorders.

The Connection Between HRV and Heart-Related Pathologies

The primary interest in HRV relates to its potential prognostic value in CVD and sudden cardiac death. Indeed, HRV independently predicts sudden death in coronary patients, and a lower HRV is associated with a subsequent 40% increase in the risk of suffering a first cardiovascular event. Overall, reduced HRV, reflecting increased SNS or reduced PNS activity, has been associated with the development of many cardiovascular conditions, including coronary artery disease, hypertension, CHF, and MI, as well as poor cardiovascular outcomes in those who already ail. Specifically, decreased HRV has been found to be an independent predictor of morbidity and mortality following MI.

 

LF/HF ratio has also been found to be inversely associated with a lifetime risk of CVD. Particularly, healthy men with decreased HRV have approximately 4% higher lifetime risk of CVD, whereas healthy women have an 8% higher lifetime risk. In addition, the rate at which CHF and arrhythmias occur has been related to a reduced HRV. Moreover, HRV may be an independent prognostic determinant for individuals with unstable angina. Hence, reduced HRV is associated with a worse prognosis in several heart-related medical conditions. Since HRV measures are simple and non-invasive, they may greatly contribute to CVD prevention.

 

A possible mechanism through which HRV influences cardiovascular health is the C-reactive protein (CRP). CRP is a protein produced by the liver as a response to inflammation. Higher CRP levels are associated with a greater risk of CVD. Whether by influencing inflammation or other mechanisms, HRV may be used as a biomarker of cardiac morbidity and mortality as well as CVD progression and future risk complications.

HRV and Diabetes

Studies suggest that an impairment of the functioning of the autonomic nervous system functioning, reflected in HRV, occurs during the early stages of diabetes and becomes progressively worse. In one study, HF-HRV, which indicates PNS activity, was lower in diabetics than in controls. It was concluded that frequency-domain measures of HRV are useful when evaluating diabetic autonomic and peripheral neuropathies. In another study, HF-HRV in non-diabetics was greater in those with lower fasting insulin levels. Thus, a relationship between insulin resistance, as indicated by higher fasting insulin levels, and lower HRV was implied. In addition, after a 9-year follow-up, there was a general decline in HRV. Overall, HRV appears to be associated inversely with plasma glucose levels.

How HRV is Related to Weight-Related Issues

It seems that obesity can alter HRV. Indeed, several studies have demonstrated an inverse association between weight gain and HRV. Notably, visceral adiposity may have a stronger association with HRV than total body fatness. In a study, an average weight loss of 3.9kg in overweight postmenopausal women was associated with an increased HRV. Also, in subjects who had undergone caloric restriction for an average of seven years, several measures of HRV metrics were significantly higher. Low cardiorespiratory fitness and higher body fatness are associated with lower HRV, with the former being the stronger determinant. Although adiposity adversely influences HRV, this effect may be reversible with weight loss and/or caloric restriction.

HRV and Psychiatric Illnesses

A dysfunctional autonomic nervous system, with an associated reduction in HRV, has been found in a wide range of psychiatric disorders, including bipolar disorder, anxiety disorders, post-traumatic stress disorder, and schizophrenia. There is also evidence that HRV indices are reduced in conditions characterized by emotional dysregulation, such as depression. When depressed patients and healthy controls were compared, the former had a lower HRV; it was particularly lower in those with more severe symptoms. Importantly, HRV can predict the onset of psychological illness ten years later. Given the links between HRV, emotion regulation, and executive functioning, it has been proposed that HRV is a biomarker of mental illness.

Key Takeaways

Research suggests HRV as a biomarker in individuals with various clinical conditions, particularly of cardiac etiology, an indicator of health in the general community and a non-invasive tool of autonomic heart rate control during physical and mental challenges. Many modifiable lifestyle factors can beneficially modulate HRV, including physical exercise and diet. Applications and devices measuring HRV are increasingly popular, particularly among athletes, to monitor different aspects of their training, including exercise performance, training adaptations, and recovery.

An Ounce of Prevention - Hyperion Health Blog

A woman is helping an older woman do exercises on an exercise ball in a gym.

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By Jesse Oswald • January 29, 2025
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Predicting Medical Costs with VO2max

By Jesse Oswald • January 20, 2025
Highlights Healthcare expenses are skyrocketing, with consumers and employers facing the significant brunt. Identifying those likely to get sick is critical as our resource-strapped healthcare system should focus on those likely to become the most significant burden to the system. VO2 max is a crucial longevity indicator that can also accurately predict healthcare expenses. The rampant chronic disease epidemic and the resulting surge in medical expenses is one of the most dire problems of modern societies, probably only second to climate change. Healthcare inflation is on a meteoric rise, and for those with limited or no healthcare coverage, a medical emergency is the equivalent of personal bankruptcy. A dire problem for employers In the US, employers and consumers who face rising health insurance premiums and astronomical out-of-pocket medical expenses feel the brunt of rising healthcare costs. Such is the problem that even large, well-capitalized corporations choose to send employees overseas for specific medical procedures since the cost of traveling and treatment in a foreign country is lower than the cost of care in the US. Another startling example is the infamous "northern caravan," a term that describes people with diabetes in the northern states who travel to Canada to secure their insulin supply. According to McKinsey , a survey conducted among over 300 employers highlighted that the average increase in the cost of health benefits over the past three years has been within the range of 6 to 7 percent. This survey also indicated that any rate increases exceeding 4 to 5 percent were deemed unsustainable. Interestingly, 95 percent of the surveyed employers expressed willingness to contemplate reducing benefits if costs surged by 4 percent or more. The primary cost-control measures that these employers indicated they might explore included elevating the portion of premium costs covered by employees and a potential transition to high-deductible health plans. Why is Breath Analysis relevant? Vis-a-vis this problem, the early and accurate estimation of who will get sick and how much they will cost is as critical as the treatment itself. The reason is that no other method of accurately identifying at-risk populations exists; it helps focus our scarce prevention resources and attention on those most in need. Breath analysis, AKA VO2max or metabolic testing, is an assessment that reveals two key biomarkers that provide significant predictive value for one's likelihood of developing costly chronic conditions. These two biomarkers are VO2max and the Respiratory Exchange Ratio. In this article, we will dive into VO2max to understand why it's a critical reflection of our overall health and, consequently, a window into our future healthcare spend. What is VO2max? Let's start with the basics. What is VO2max? VO2 max is the maximum amount of oxygen the human body can absorb. It is measured in terms of milliliters of oxygen consumed per kilogram of body weight. The below formula below indicates how VO2max is calculated: The numerator indicates the volume of oxygen your heart, lungs, and cells can absorb, expressed in milliliters per minute. The denominator indicates the weight of the individual represented in kilograms. 
There are many different types of fats in this picture.

Dietary Fat: An Essential Dietary Component Rather than the root of all Nutritional Health Issues

By Jesse Oswald • January 13, 2025
Key points A total fat intake between 20-35% ensures sufficient intake of essential fatty acids and fat-soluble vitamins Omega-6 PUFAs are primarily found in vegetable oils, while omega-3 PUFAs are primarily found in fatty fish and fish oils Both omega-3 PUFAs and MUFAs have established benefits for cardiovascular disease TFAs are the only dietary lipids that have a strong positive relationship with cardiovascular disease Omega-3 PUFA supplementation increases the beneficial bacteria of the human microbiome Over the last three decades, there has been a great revolution against fat due to its suspected association with several nutritional health issues, especially cardiovascular disease. There was a tremendous amount of evidence that indicated dietary cholesterol and saturated fat as the main culprits of cardiovascular disease, thus morbidity and mortality. It was when all the low-fat and no-fat dairy products started to launch, promising even complete substitution of the cholesterol-lowering heart medication if these products were exclusively consumed. Let’s start from the beginning. Dietary fat intake can vary significantly and still meet energy and nutrient needs. International guidelines suggest a total fat intake between 20% and 35% of the daily caloric consumption. This range ensures sufficient intake of essential fatty acids and fat-soluble vitamins. Not only does the quantity of the ingested fat matter, but most importantly, its quality. Some dietary fats have beneficial effects, with a significant role in maintaining good health, while others may threaten it. Which are, after all, the dietary fats? Dietary fats is a rather heterogeneous group of organic compounds, including four main types of fat, which are elaborately described in the following sections of this article. Polyunsaturated fatty acids (PUFAs) Polyunsaturated fatty acids (PUFAs) have two or more carbon-carbon double bonds. Omega-6 PUFAs and omega-3 PUFAs are the main types of PUFAs and are classified according to the location of the first unsaturated bond (sixth and third carbon atom, respectively). Alpha-Linolenic acid (ALA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and eicosapentaenoic acid (EPA) are the most important omega-3 PUFAs. ALA is an essential fatty acid that can only be obtained from diet and can be converted into EPA and then to DHA, but the rate of this conversion is finite, approximately 7.0%–21% for EPA and 0.01%–1% for DHA. In the same way, the most important omega-6 PUFAs are linoleic acid (LA) and arachidonic acid (ARA). LA is an essential fatty acid that, in order to give rise to ARA, needs to be ingested through the diet as the human body cannot synthesize it. The recommended intake for total PUFA ranges between 5% and 10% of the total energy intake, while a total omega-3 PUFA intake of 0.5%–2% and a total omega-6 PUFA intake of 2.5%-5% is suggested. A dietary ratio of omega−6/omega−3 PUFA is recommended to be 1:1–2:1 to balance their competing roles and achieve health benefits. Omega-6 and omega-3 PUFAs Omega-6 PUFAs, in the form of LA, are plentiful in most crop seeds and vegetable oils, such as canola, soybean, corn, and sunflower oils. In contrast to omega-6 PUFAs, omega-3 PUFAs are obtained from a limited range of dietary sources. Flax, chia, and perilla seeds are rich in ALA, with significant amounts also detected in green leafy vegetables. The consumption of fatty fish, such as salmon, sardines, tuna, trout, and herring, provides high amounts of EPA and DHA. Besides fish and their oils, small amounts of omega-3 PUFAs are also detected in red meat like beef, lamb, and mutton. All the above dietary sources provide EPA, DPA, DHA, LA, and ARA in different amounts, and their intake is necessary for normal physiological function. PUFAs play a critical role in many chronic diseases, affecting human cells by regulating inflammation, immune response, and angiogenesis. Omega-3 PUFAs’ role against hypertriglyceridemia has been clarified, and research indicates that systematically consuming oily fish can contribute to general heart protection. Supplementation with omega-3 PUFAs could potentially lower the risk of several cardiovascular outcomes, but the evidence is stronger for individuals with established coronary heart disease. Moreover, adequate EPA and DHA levels are necessary for brain anatomy, metabolism, and function. Although the mechanisms underlying omega-3 PUFAs' cardioprotective effects are still poorly understood, several studies have been conducted in this direction. Unfortunately, that does not hold true for their omega-6 counterparts, for which controversial emerging data tend to show anti-inflammatory behavior that needs to be further studied. Monounsaturated fatty acids (MUFAs) In contrast to PUFAs, monounsaturated fatty acids (MUFAs) are easily produced by the liver in response to the ingestion of carbohydrates. The main MUFA is oleic acid, found in plant sources, such as olive oil, olives, avocado, nuts, and seeds, while minimal amounts are also present in meat, eggs, and dairy products. Specific guidelines around MUFAs’ dietary consumption do not exist. Therefore, MUFAs are recommended to cover the remaining fat intake requirements to reach the total daily fat intake goal. A growing body of research shows that dietary MUFAs reduce or prevent the risk of metabolic syndrome, cardiovascular disease (CVD), and hypertension by positively affecting insulin sensitivity, blood lipid levels, and blood pressure, respectively. Moreover, olive oil contains several bioactive substances, possessing anti-tumor, anti-inflammatory, and antioxidant qualities. According to a meta-analysis, consuming olive oil was linked to a lower risk of developing any sort of cancer, especially breast cancer and cancer of the digestive system. Another study found that an isocaloric replacement of 5% of the energy from saturated fatty acids (SFAs) with plant MUFAs led to an 11% drop in cancer mortality over a 16-year follow-up period. Therefore, including MUFAs in the everyday diet offers multifaceted benefits in chronic disease prevention and management, including cancer and general health promotion.  Saturated fatty acids (SFAs) Saturated fatty acids (SFAs) form a heterogeneous group of fatty acids that contain only carbon-to-carbon single bonds. Whole-fat dairy, (unprocessed) red meat, milk chocolate, coconut, and palm kernel oil are all SFA-rich foods. These fatty acids have distinct physical and chemical profiles and varying effects on serum lipids and lipoproteins. Stearic, palmitic, myristic, and lauric acids are the principal SFAs found in most natural human diets. Dietary practice and guidelines recommend limiting SFA intake to <10% of the total energy (E%), while the American Heart Association suggests an even lower intake of <7 E% because total saturated fat consumption and LDL-C levels are positively correlated. However, the role of SFAs in CVDs is quite complex, and the evidence is heterogeneous. In a recent study with a 10.6-year follow-up period, which included 195,658 participants, there was no proof that consuming SFAs was linked to developing CVD while replacing saturated fat with polyunsaturated fat was linked to an increased risk of CVD. Moreover, according to 6 systematic reviews and meta-analyses, cardiovascular outcomes and total mortality were not significantly impacted by substituting saturated fat with polyunsaturated fat. Even if these analyses were to be challenged, due to heterogenous evidence, the possible reduction in CVD risk associated with replacing SFAs with PUFAs in several studies may not necessarily be an outcome of SFAs’ negative effect but rather a potential positive benefit of PUFAs. Regarding SFAs' effect on different types of cancers, associations of their intake with an increased risk of prostate and breast cancer have been indicated. Conversely, a meta-analysis showed no link between SFA intake and a higher risk of colon cancer; similarly, consuming MUFAs, PUFAs, or total fat did not affect colon cancer risk. Hence, the role of SFA consumption in preventing, promoting, or having a neutral role in serious chronic diseases has not been fully elucidated yet. Trans fatty acids (TFAs) Trans fatty acids (TFAs) are created industrially by partially hydrogenating liquid plant oils or can be naturally derived from ruminant-based meat and dairy products. TFAs are highly found in commercial baked goods, biscuits, cakes, fried foods, etc. Guidelines regarding TFAs are stringent and limit TFA intake to <1% of energy or as low as possible. In 2015, the US Food and Drug Administration declared that industrial TFAs are no longer generally recognized as safe and should be eliminated from the food supply as their consumption is strongly linked to various CVD risk factors. Specifically, TFA intake raises triglycerides and increases inflammation, endothelial dysfunction, and hepatic fat synthesis, leading to a significantly increased risk of coronary heart disease (CHD). A meta-analysis suggested that increased TFA intake led to an increase in total and LDL-cholesterol and a decrease in HDL-cholesterol concentrations. Data also indicates that TFAs may influence carcinogenesis through inflammatory pathways, but the reported data are debatable. A recent study investigated the effects of all types of dietary fat intake on CVD risk. While PUFA, MUFA, and SFA intake were not linked to higher CVD risk, dietary TFA intake showed a strong association with CVD risk. Analysis indicated PUFA intake and CVD risk were inversely correlated, and the relative risk of CVD was reduced by 5% in studies with a 10-year follow-up. Dietary lipids and the human microbiome Dietary lipids also affect human microbiota composition. Studies have identified a close association between the human microbiome and metabolic diseases, including obesity and type 2 diabetes. Diets with a high omega-6 PUFA, SFA, and TFA intake increase the amount of many detrimental bacteria in the microbiome and reduce the amount of the beneficial ones, altering the microbiota composition and inducing inflammation via the secretion of pro-inflammatory cytokines. These bacteria may disrupt the gut barrier function, allowing lipopolysaccharides (LPS) translocation, which are bacterial toxins. This condition is linked to metabolic perturbations such as dyslipidemia, insulin resistance, non-alcoholic fatty liver disease (NAFLD), and CVD. On the contrary, omega-3 PUFA (EPA and DHA) supplementation increases beneficial bacteria and limits harmful ones, enhancing intestinal barrier functioning and preventing LPS translocation and its implications. Omega-3 PUFA supplementation has also been studied as a means of mental health disorders management, but the evidence is still controversial. A possible protective impact of fish consumption on depression has been suggested by various studies, as well as a possible protective effect of dietary PUFAs on moderate cognitive impairment. A recent review of meta-analyses indicated that omega-3 PUFA supplementation might have potential value in mental health disorders, but data credibility is still weak. Dietary lipids and obesity Last but not least, obesity and its management is another field that dietary lipids intake seems to impact with their mechanisms. A diet high in PUFA has been shown to lower the total mass of subcutaneous white adipose tissue (the predominant fat type in human bodies), reduce blood lipid levels, and improve insulin sensitivity. In a study comparing PUFA and MUFA isocaloric intake, PUFA was more advantageous and lowered visceral adiposity in patients with central obesity. By stimulating brown adipose tissue, which aids energy expenditure through its elevated thermogenic activity, omega-3 PUFAs seem to elicit these positive effects in fat tissue, thus being useful in preventing and/or managing obesity. Another related study compared PUFA to SFA overfeeding in dietary surplus conditions that aimed to increase weight by 3%. While SFA overfeeding led to weight gain, primarily through the expansion of the visceral adipose tissue, PUFA overfeeding also led to weight gain, but because of a greater expansion of lean tissue mass. To sum up, dietary fats are an essential part of the human diet with many important physiologic functions, including cell function, hormone production, energy, and nutrient absorption. Moreover, dietary fat consumption is associated with positive outcomes in regard to cardiovascular disease, metabolic syndrome, cancer, and depression. Therefore, there is no reason to demonize this valuable dietary component, incriminating it for irrelevant adverse health outcomes, primarily weight loss failure and obesity. References 1. Astrup A, Magkos F, Bier DM, Brenna JT, de Oliveira Otto MC, Hill JO, King JC, Mente A, Ordovas JM, Volek JS, Yusuf S, Krauss RM. Saturated fats and health: A reassessment and proposal for food-based recommendations: JACC State-of-the-Art review. J Am Coll Cardiol. 2020;76(7):844-857. DOI: 10.1016/j.jacc.2020.05.077 2. Bojková B, Winklewski PJ, Wszedybyl-Winlewska M. Dietary fat and cancer-Which is good, which is bad, and the body of evidence. Int J Mol Sci. 2020;21(11):4114. DOI: 10.3390/ijms21114114 3. Custers, Emma EM, Kiliaan, Amanda J. Dietary lipids from body to brain. Prog Lipid Res. 2022;85:101144. DOI: 10.1016/j.plipres.2021.101144 4. de Souza RJ, Mente A, Maroleanu A, Cozma AI, Ha V, Kishibe T, Uleryk E, Budylowski P, Schünemann H, Beyene J, Anand SS. Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies. BMJ. 2015;351:h3978. DOI: 10.1136/bmj.h3978 5. Gao X, Su X, Han X, Wen X, Cheng C, Zhang S, Li W, Cai J, Zheng L, Ma J, Liao M, Ni W, Liu T, Liu D, Ma W, Han S, Zhu S, Ye Y, Zeng F-F. Unsaturated fatty acids in mental disorders: An umbrella review of meta-analyses. Adv Nutr. 2022;13(6):2217-2236. DOI: 10.1093/advances/nmac084 6. Liu AG, Ford NA, Hu FB, Zelman KM, Mozaffarian D, Kris-Etherton PM. A healthy approach to dietary fats: understanding the science and taking action to reduce consumer confusion. Nutr J. 2017;16(1):53. DOI: 10.1186/s12937-017-0271-4 7. Poli A, Agostoni C, Visioli F. Dietary fatty acids and inflammation: Focus on the n-6 series. Int J Mol Sci. 2023;24(5):4567. DOI: 10.3390/ijms24054567 8. Saini RK, Keum Y-S. Omega-3 and omega-6 polyunsaturated fatty acids: Dietary sources, metabolism, and significance-A review. Life Sci. 2018;203:255-267. DOI: 10.1016/j.lfs.2018.04.049 9. Saini RK, Prasad P, Sreedhar RV, Naidu KA, Shang X, Keum Y-S. Omega-3 polyunsaturated fatty acids (PUFAS): Emerging plant and microbial sources, oxidative stability, bioavailability, and health benefits-A review. Antioxidants (Basel). 2021;10(10):1627. DOI: 10.3390/antiox10101627 10. Zhao M, Chiriboga D, Olendzki B, Xie B, Li Y, McGonigal LJ, Maldonado-Contreras A, Ma Y. Substantial increase in compliance with saturated fatty acid intake recommendations after one year following the American Heart Association diet. Nutrients. 2018;10(10):1486. DOI: 10.3390/nu10101486 11. Zhu Y, Bo Y, Liu Y. Dietary total fat, fatty acids intake, and risk of cardiovascular disease: a dose-response meta-analysis of cohort studies. Lipids Health Dis. 2019;18:91. DOI: 10.1186/s12944-019-1035-2
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