Starting with our first cohort on January 1, 2025, we are going to work with volunteers to study this. If you want to raise or better understand your T-levels, be sure to sign up (we'll provide next steps over email for anyone interested):

We are going to do this study a bit differently that most academic research is done. It will be totally open source - users will submit data anonymously but publicly so anyone can verify our findings or publish research based on the data. The costs are minimal - you just need to pay for two testosterone blood tests, which is about $150 total. If you have issues paying, please sign up anyway and email info@shaperresearch.org and we will see if any sponsors are able to help.

What does the study entail?

1. You will get a T test and fill out a survey on your lifestyle habits.

2. Our research team and our team’s physician will review the test and survey results. You will receive a personalized plan to improve your T levels.

3. For the next twelve weeks, you will fill out a weekly survey that asks you about your lifestyle and if you have been following the plan provided

   1. For people that use wearables (like Whoop), you will be asked to submit this data as well (we’ll provide tooling for this to make the process simple)

4. At the end, you will test your T again

5. We will then analyze the data and publish both the data and our own findings

Your treatment plans will vary person to person, but the main categories we are targeting are:

• Dietary Adjustments:

  • Emphasis on a balanced diet with healthy fats, adequate protein, and reduction of processed foods and sugars.

  • Supplementation with Vitamin D, zinc, magnesium,.

• Exercise Regimen:

  • Strength training and cardio sessions tailored to individual fitness levels and need for fat loss.

• Stress Management:

  • Implementation of stress reduction techniques, including mindfulness, meditation, and breathing exercises.

• Sleep Improvement:

  • Establishing sleep hygiene practices to ensure 7-9 hours of quality sleep with consistent bed/wake times.

    • Nighttime protocol (blue light glasses, wind-down time, etc)

• Environmental Adjustments:

  • Reducing exposure to endocrine disruptors and ensuring access to clean water and natural sunlight.

• Behavioral Changes:

  • Encouraging social interactions, regular sexual activity, and avoiding smoking and excessive alcohol consumption.

Who should sign up?

Any man over the age of 18 who wants to be healthier or help us better understand the human body. If you use Whoop, we will prioritize your application, as we are building tooling to analyze this data as well.

Subscribe now

Testosterone has been a more and more prevalent topic of conversation - Joe Rogan, Andrew Huberman, and other mainstream media figures have openly talked about using testosterone replacement therapy to raise their testosterone levels. It’s widely speculated that Jeff Bezos, who gained a lot of muscle mass in his 50s, also used TRT. It’s natural that testosterone can decrease when you age. However testosterone levels are decreasing over time, and at a quite alarming rate. This trend has been noted by multiple studies, with the first and most notable study published in The Journal of Clinical Endocrinology & Metabolism by Travison et al. (2007) and results summarized in Figures 1 and 2 below.

• Testosterone levels are dropping and have been steadily since they have been measured. These changes are significant - with a close to 25% drop in average T levels in the 25 years between the first and last cohort

• Testosterone is also dropping faster as people age - so not only are people entering middle age with less T, they are losing the T they have faster. This is shown most clearly in Figure 1 (line labeled T3)

When you expand your view to look at the T levels of people born at different times, the reduction in total testosterone over time becomes even more apparent. Looking at 65yo men born in 1945 versus 1920, their T is on average 30% lower.

Having low testosterone doesn’t sound good, but exactly how impactful is low T for most men? Short answer - very impactful. Testosterone has numerous effects throughout the body including an impact on metabolic pathways, so deficiency of testosterone will hurt you everywhere. Testosterone helps increase insulin sensitivity - regulating the uptake of sugar, weight gain, and body fat. There’s a complicated and bidirectional relationship between testosterone and body fat. Low testosterone will lead to obesity through insulin resistance, but obesity itself leads to an increase in expression of the enzyme aromatase, which will convert testosterone to estrogen, lowering testosterone and furthering the cycle. It’s a vicious cycle no one wants to get caught in.

To imagine the systemic effects of testosterone on every cell in your body think of differences between typical male and female phenotypes. They’re largely due to hormonal differences, especially during critical developmental years with higher androgen receptor count and sensitivity. Testosterone increases muscle mass, it increases red blood cell production, and it increases bone density. Testosterone also has neuro-psychiatric effects relating to mood, focus, energy level, sex drive, sleep, and pretty much everything your brain does. Low testosterone will make it hard to sleep, it’ll make it hard to experience sexual arousal, and you’ll probably feel bad. It is largely the effect of androgens like testosterone that physically and mentally differentiates us into men as we develop and keeps us that way. Deficiency of testosterone leads to the absence of these defining characteristics. We are just beginning to feel the impact on chronic disease and lifespan.

If a man’s total testosterone levels are far below normal (the medical community commonly defines this threshold as less than 300 nanograms per deciliter), this is considered hypogonadism. Most doctors will prescribe supplemental testosterone replacement therapy at these levels, otherwise quality of life is greatly reduced. However most men will still feel a strong effect from higher or lower T levels, even if they are well within normal range.

The Research

Thankfully, there has been extensive and occasionally conclusive research on what environmental and lifestyle factors effect testosterone levels. As always, we’ve assembled some of the most relevant recent papers on the topic, linked below. The main factors most people should be concerned about are:

1. Exercise (Intensity and Strength Training)

2. Diet

3. Sleep

4. Vitamin Supplements

   1. Vitamin D

   2. Zinc & Copper

   3. Ashwagandha

Below we include a couple papers that dive into each area, as well as a few more that investigate combined effects, or are otherwise interesting. The last paper we link was a fun one, as you might imagine given the authors research focus is on drunk, jacked rats:

Exercise

Different responses of selected hormones to three types of exercise in young men.

Journal: European Journal Of Applied Physiology

Authors: Keith A Stokes, Kate L Gilbert, George M Hall, Robert C Andrews, Dylan Thompson

Publication Date: 2013-08-23

SHAPER's Take: You just gotta lift heavy. Stokes et al. provide insights into natural methods to boost hormone levels through various forms of exercise, highlighting that resistance exercise, of the types tested, significantly ramps up testosterone production in men. This research is particularly compelling as it differentiates how specific exercise modalities distinctly influence hormones like testosterone, useful for individuals seeking natural ways to enhance their hormonal health. The real-world relevance lies in helping men choose appropriate exercises for targeted hormonal benefits, potentially improving their overall well-being without pharmacological interventions.

Acute hormonal and neuromuscular responses to hypertrophy, strength and power type resistance exercise.

Journal: European Journal Of Applied Physiology

Authors: Grant O McCaulley, Jeffrey M McBride, Prue Cormie, Matthew B Hudson, James L Nuzzo, John C Quindry, N Travis Triplett

Publication Date: 2009-05-04

SHAPER's Take: Ok so you are lifting heavy - what exercises should you do? It turns out the body builders (or as we like to call them, “mass monsters”) were right on this one. While using machines in the gym will still positively improve your health, free weights provide a stronger result w.r.t hormone levels. Many weightlifting experts will also recommend free weights for muscle growth, strength, and injury prevention. McCaulley et al. demonstrate that hypertrophy-focused resistance training, characterized by moderate weights and higher repetitions, notably raises testosterone levels immediately following exercise, compared to strength or power regimens with heavier weights or explosive movements. This paper suggests that for men looking to naturally boost their hormone levels, adjusting their workout style to include more hypertrophic exercise could be advantageous. This insight is particularly valuable for those interested in optimizing hormonal health through exercise, rather than relying on synthetic alternatives

Effects of strongman training on salivary testosterone levels in a sample of trained men.

Journal: Journal Of Strength And Conditioning Research

Authors: Jamie J Ghigiarelli, Katie M Sell, Jessica M Raddock, Kurt Taveras

Publication Date: 2013-11-18

SHAPER's Take: This is a very practically useful paper as it lays out specific exercises that will maximize your T levels. Ever seen the “World’s Strongest Man”? Well, basically do that:

Ghigiarelli et al.'s research demonstrates how strongman and hypertrophic training protocols can significantly boost testosterone levels, with hypertrophic routines showing the highest spike. This insight is particularly valuable for individuals seeking natural methods to enhance testosterone, which is linked to improved muscle mass, energy levels, and overall health. The study provides a useful comparison of exercise impacts on hormonal responses, suggesting practical workouts that the average person could incorporate to manage or increase their testosterone naturally.

The effect of resistive exercise rest interval on hormonal response, strength, and hypertrophy with training.

Journal: Journal Of Strength And Conditioning Research

Authors: Robert Buresh, Kris Berg, Jeffrey French

Publication Date: 2009-05-05

SHAPER's Take: If you don’t have a giant tire on hand - don’t worry. Most people will see strong results from all sorts of different strength training regimens. Buresh et al.'s findings focuses on the impact of rest intervals during resistance training on hormonal fluctuations, particularly testosterone, in initially untrained males. While they replicate previous findings about shorter-rest intervals giving higher acute hormonal responses over the first few weeks of training, this effect doesn’t persist in the long-term. There are a series of similar results across other articles.

The takeaway? - No need to autistically micromanage every tiny detail of your training schedule. Rest intervals are not a huge deal, hormonally at least. The key point is to lift heavy and make sure you get in the gym on a regular basis. Consistency is king.

Diet

Effects of Ketogenic Dieting on Body Composition, Strength, Power, and Hormonal Profiles in Resistance Training Men.

Journal: Journal Of Strength And Conditioning Research

Authors: Jacob M Wilson, Ryan P Lowery, Michael D Roberts, Matthew H Sharp, Jordan M Joy, Kevin A Shields, Jeremy M Partl, Jeff S Volek, Dominic P D'Agostino

Publication Date: 2021-04-02

SHAPER's Take: Diet is important to hormone levels as well. Eating a healthy, high-protein diet supports fat loss and post-workout recovery. Higher body fat has been shown to discourage testosterone production. Wilson et al. demonstrate that a ketogenic diet paired with resistance training not only supports favorable body composition by increasing lean body mass and decreasing fat mass but also naturally boosts testosterone levels in resistance-trained men. This insight can guide individuals looking to enhance muscle growth, strength, and hormonal health through dietary adjustments.

Very low-calorie ketogenic diet rapidly augments testosterone levels in non-diabetic obese subjects.

Journal: Andrology

Authors: Angelo Cignarelli, Daniele Santi, Valentina Annamaria Genchi, Eleonora Conte, Fiorella Giordano, Simona Di Leo, Annalisa Natalicchio, Luigi Laviola, Francesco Giorgino, Sebastio Perrini

Publication Date: 2023-01-17

SHAPER's Take: Very overweight people tend to have very low testosterone, often far below healthy levels, a condition known as hypogonadism. The key question is how to break this cycle, because calorie restriction results in even more severe testosterone level drops in the short-term.

Cignarelli et al.'s research demonstrates a way around this, measuring a rapid and significant increase in testosterone levels through a very low-calorie ketogenic diet in obese non-diabetic men. This highlights a potentially effective dietary strategy for managing functional hypogonadism associated with obesity. Their findings suggest that dietary modifications alone can play a pivotal role in hormonal balance, offering an accessible intervention for improving testosterone levels without pharmacological means. This approach could be particularly beneficial for men seeking natural methods to enhance hormonal health and reverse obesity-related hormonal imbalances.

Neither soy nor isoflavone intake affects male reproductive hormones: An expanded and updated meta-analysis of clinical studies.

Journal: Reproductive Toxicology (Elmsford, N.Y.)

Authors: Katharine E Reed, Juliana Camargo, Jill Hamilton-Reeves, Mindy Kurzer, Mark Messina

Publication Date: 2021-10-28

SHAPER's Take: We’re still gonna call people “soy boys” if we want to. However, the link between soy consumption and reduced T levels is very weak to non-existent. Reed et al.'s research is significant as it clarifies the misconception that soy products and isoflavones adversely affect male hormone levels, confirming that consuming soy does not lead to decreased testosterone or altered estrogen levels in men. The study is noteworthy for debunking widespread myths about the feminizing effect of soy on male reproductive health, thereby providing reassurance to consumers about the inclusion of soy in a balanced diet. Regarding naturally increasing testosterone levels in men, it's essential to focus on well-supported lifestyle and dietary practices. Regular physical activity, particularly strength training and high-intensity interval training, has been shown to boost testosterone levels effectively. Adequate sleep, stress management, maintaining a healthy weight, and a balanced diet rich in vitamins and minerals also contribute to optimal testosterone production.

Sleep

Sleep deprivation lowers reactive aggression and testosterone in men.

Journal: Biological Psychology

Authors: Kimberly A Cote, Cheryl M McCormick, Shawn N Geniole, Ryan P Renn, Stacey D MacAulay

Publication Date: 2013-08-20

SHAPER's Take: Much of your body’s testosterone is produced when you sleep. That’s why when you get a T-test, most testing facilities require you do so in the morning. It’s not surprising then that sleep deprivation can greatly lower testosterone levels. Cote et al.'s findings are crucial in highlighting the significant impact of adequate sleep on maintaining hormonal balance and reducing aggressive responses in men. This research is particularly relevant for the general population as it underscores the potential of proper sleep hygiene to naturally regulate testosterone levels and modulate behavior, providing a non-pharmaceutical strategy to enhance mental and physical health.

The cost of the circadian desynchrony on the Leydig cell function.

Journal: Scientific Reports

Authors: Maja V Pavlovic, Dijana Z Marinkovic, Silvana A Andric, Tatjana S Kostic

Publication Date: 2022-09-19

SHAPER's Take: Pavlovic et al.'s research highlights the negative impact of irregular light exposure, resembling shift work, on testosterone production in rats. By demonstrating how disrupted sleep patterns can lead to decreased testosterone levels through mitochondrial dysfunction in Leydig cells, this study provides insight into natural ways men might enhance their testosterone levels by maintaining regular circadian rhythms. This could be particularly useful for shift workers or those with irregular sleep schedules seeking to improve their hormonal health.

Vitamins

Influence of Sunlight and Oral D₃ Supplementation on Serum 25(OH)D Concentration and Exercise Performance in Elite Soccer Players.

Journal: Nutrients

Authors: Małgorzata Magdalena Michalczyk, Artur Gołaś, Adam Maszczyk, Piotr Kaczka, Adam Zając

Publication Date: 2021-02-17

SHAPER's Take: Michalczyk et al.'s research demonstrates that exposure to sunlight and supplementation with vitamin D can significantly increase serum vitamin D and testosterone levels in elite soccer players. This suggests that similar strategies could be employed by the average man to naturally enhance testosterone levels, potentially improving physical performance and overall hormonal health. This study underlines the importance of maintaining adequate vitamin D levels for hormonal balance and athletic performance, indicating a straightforward intervention for testosterone management through lifestyle and dietary changes.

Effect of oral zinc therapy on gonadal function in hemodialysis patients. A double-blind study.

Journal: Annals Of Internal Medicine

Authors: S K Mahajan, A A Abbasi, A S Prasad, P Rabbani, W A Briggs, F D McDonald

Publication Date: 1982-10-21

SHAPER's Take: Mahajan et al.'s research demonstrates that zinc supplementation can significantly enhance testosterone levels, as well as sperm count and quality, in hemodialysis patients, indicating a simple, nutrient-based approach may be beneficial for managing hypogonadism in this population. This finding suggests potential broader implications for non-uremic individuals seeking natural methods to improve their gonadal function and general reproductive health. Further exploration might reveal whether similar benefits can be realized in the general male population, offering a non-pharmacological option to boost testosterone naturally.

Correlation between serum testosterone level and concentrations of copper and zinc in hair tissue.

Journal: Biological Trace Element Research

Authors: Chung Soo Chang, Jong Bo Choi, Hae Jin Kim, Sat Byul Park

Publication Date: 2012-04-27

SHAPER's Take: Chang et al.'s research reveals significant links between trace minerals in the body and testosterone levels, highlighting that higher zinc levels are associated with normal testosterone levels, while elevated copper and copper/zinc ratios are connected with reduced testosterone. This finding offers a potentially natural method for managing testosterone levels through dietary adjustments, emphasizing the influence of nutrient intake on hormonal health. This insight can guide individuals in modifying their diet to possibly enhance or maintain their testosterone levels naturally without pharmacological interventions.

Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial.

Journal: Journal Of The International Society Of Sports Nutrition

Authors: Sachin Wankhede, Deepak Langade, Kedar Joshi, Shymal R Sinha, Sauvik Bhattacharyya

Publication Date: 2016-08-16

SHAPER's Take: While “natural supplements” are mostly charlatan nonsense and occasionally just poison, it seems like ashwagandha has some pretty strong effects across the ~60 people or so studied here. Wankhede et al.'s findings demonstrate that ashwagandha supplementation can significantly enhance muscle strength and recovery while boosting testosterone levels in men undertaking resistance training. This suggests a natural, plant-based approach to potentially augment fitness outcomes and hormonal balances, providing a beneficial option for men seeking improvements in these areas without synthetic interventions. The increase in testosterone may particularly appeal to those dealing with low levels, offering a non-prescription method to manage and improve their hormonal health.

More studies

Here are a few other studies that support the ones above that we also thought were interesting, or show combined effects like the following study on military boot camp participants.

Depressed Physical Performance Outlasts Hormonal Disturbances after Military Training.

Journal: Medicine And Science In Sports And Exercise

Authors: Håvard Hamarsland, Gøran Paulsen, Paul A Solberg, Ole Gunnar Slaathaug, Truls Raastad

Publication Date: 2019-05-03

SHAPER's Take: This paper highlights the physical and hormonal impacts of extreme exercise, specifically showing that intensive military training can sharply decrease testosterone levels while increasing cortisol. Basically, while lifting is good for T levels, if you push yourself too far, your T can fall off a cliff. Reacher star Alan Ritchson has claimed this happened to him and he had to start TRT to get healthy again. For the average man seeking natural ways to enhance testosterone levels, understanding the negative hormonal impacts of excessive physical stress might encourage more balanced exercise routines and ample recovery periods to maintain or boost testosterone. This study serves as a compelling reminder of the need for moderation in training intensities and durations to prevent counterproductive effects on key hormone levels.

Salivary hormonal values from high-speed resistive exercise workouts.

Journal: Journal Of Strength And Conditioning Research

Authors: John F Caruso, Brant M Lutz, Mark E Davidson, Kyle Wilson, Chris S Crane, Chrsity E Craig, Tim E Nissen, Melissa L Mason, Michael A Coday, Robert J Sheaff, William T Potter

Publication Date: 2012-06-13

SHAPER's Take: This is one of many studies that show how intense exercise can increase T-levels. While salivary testing is less accurate than blood testing, these results show that even with higher variance data collection, you can still see stark results - a 10-20% increase post-exercise. Notably, these changes were not seen in women. Caruso et al.'s research demonstrates a notable increase in testosterone levels following high-speed resistive exercise in men, suggesting that brief, intense workouts could naturally elevate testosterone. This finding is particularly valuable for men looking to enhance their hormonal health without prolonged or excessive training regimens. Further, the study highlights the practicality of using salivary assays for hormonal monitoring, which could simplify the process for individuals regularly tracking these changes.

Sociodemographic, lifestyle and medical influences on serum testosterone and sex hormone-binding globulin in men from UK Biobank.

Journal: Clinical Endocrinology

Authors: Bu B Yeap, Ross J Marriott, Leen Antonio, Shalender Bhasin, Adrian S Dobs, Girish Dwivedi, Leon Flicker, Alvin M Matsumoto, Claes Ohlsson, Eric S Orwoll, Suchitra Raj, Christopher M Reid, Dirk Vanderschueren, Gary A Wittert, Frederick C W Wu, Kevin Murray

Publication Date: 2021-08-18

SHAPER's Take: This was a large study, with 200k+ participants. Showing the population level correlations that BMI, diet, and activity levels have with T, the experimental results in other papers are shown on a broad scale here. There are some other interesting correlations shown. For instance, having a partner or going to college both inversely correlate with T levels. However, these two correlations are less actionable for most men who wouldn’t want to get a divorce or try to “forget” college to increase T levels. Yeap et al.'s research underscores how lifestyle choices and social factors affect testosterone levels in middle-aged men. By highlighting that diet, physical activity, and body mass index (BMI) have significant impacts on testosterone, the study suggests practical pathways for men to naturally enhance their testosterone levels through modifiable behaviors. Moreover, the insights into sociodemographic correlations offer a broader perspective for personalized health strategies tailored to individual circumstances.

Postresistance exercise ethanol ingestion and acute testosterone bioavailability.

Journal: Medicine And Science In Sports And Exercise

Authors: Jakob L Vingren, David W Hill, Harsh Buddhadev, Anthony Duplanty

Publication Date: 2014-05-27

SHAPER's Take: Normally, alcohol consumption has mostly negative health effects. Many studies show that chronic alcohol consumption can lower T levels significantly. However it seems that having 4-5 beers after you work out can improve testosterone levels temporarily. Vingren et al.'s research reveals that consuming alcohol after resistance exercise may temporarily increase testosterone levels during recovery. The study size was small - but the results were stark, so still statistically significant.

Every so often new articles appear to warn people about the dangers of energy drinks appear, like this one in the New York Post from two weeks ago. And every so often a younger person has a heart attack after drinking energy drinks, as happened for 5% of the sudden cardiac arrest survivors from the Mayo Clinic study referenced in the article.

Caffeine alone is known to increase your heart rate and activate the “fight or flight” side of your nervous system. Caffeine alone can cause abnormal heart rhythms leading to heart attacks in high enough doses. Is that all that’s going on here? Are people caffeinating themselves to death, or is there something in these drinks that makes them worse than an equivalent amount of caffeine from coffee?

The Research

Lots of studies have shown that energy drinks are associated with bad health outcomes. Most of these are anecdotal or observational studies, though, which are challenged with properly adjusting for the cohort differences like poor sleep, poor dental hygiene, problematic alcohol use, and depression that are commonly associated with energy drink use. It’s hard to study fatal cardiac events after caffeine vs. “equivalent caffeine from energy drink” because it’s a relatively rare occurrence and there are too many real world confounding factors in observational data.

What you can do, though, is give people lower doses of caffeine vs. “equivalent caffeine from energy drink” and see what their heart does.

We found several studies which took this approach and looked at the impact of energy drinks on the heart. These studies found significant differences in repolarization - recovery of the heart’s electrical system after it squeezes - when consuming energy drinks versus equivalent caffeine alone. An increase in “extrasystoles” (extra heart contractions) was found for energy drinks versus equivalent caffeine alone as well.

As no other energy drink ingredients are linked with toxicity at the levels commonly consumed, these results indicate that there is some ingredient commonly found in energy drinks that acts synergistically with caffeine to alter the activity of your heart in concerning ways. There is some conjecture in the medical community that this may be taurine, which is commonly included at very high levels in energy drinks (2 grams per 16oz Monster). Although there have been no studies on the heart’s electrical system after the synergistic combination of caffeine and taurine, studies have shown that taurine independent of caffeine also increases heart arrhythmia in animal studies and has a synergistic impact with caffeine on athletic and cognitive performance, so there is certainly support for this hypothesis.

We also included one interesting and incredibly large observational study from South Korea showing a higher incidence of asthma and allergy symptoms in those who consume energy drinks. More research is needed here, but perhaps another reason to avoid energy drinks until more research is done.

While the causal relationship with energy drinks and the hearts electric system is not well understood, there are statistically significant correlations between energy drink consumption and serious heart issues. Unless you really like energy drinks, we’d stick with coffee and tea.

Randomized Controlled Trial of High-Volume Energy Drink Versus Caffeine Consumption on ECG and Hemodynamic Parameters.

Journal: Journal Of The American Heart Association

Authors: Emily A Fletcher, Carolyn S Lacey, Melenie Aaron, Mark Kolasa, Andrew Occiano, Sachin A Shah

Publication Date: 2018-03-05

SHAPER's Take: Fletcher et al.'s research underscores the cardiac risks linked to high-volume energy drink consumption compared to similar caffeine levels in coffee or other caffeinated drinks, revealing significant changes in the heart's electrical activity and blood pressure. This evidence highlights a critical need to scrutinize the non-caffeine components of energy drinks, the effects of which are poorly understood (especially in conjunction with caffeine).

Abstract: Caffeine in doses <400 mg is typically not considered arrhythmogenic, but little is known about the additional ingredients in energy drinks. We evaluated the ECG and blood pressure (BP) effects of high-volume energy drink consumption compared with caffeine alone. This was a randomized, double-blind, controlled, crossover study in 18 young, healthy volunteers. Participants consumed either 946 mL (32 ounces) of energy drink or caffeinated control drink, both of which contained 320 mg of caffeine, separated by a 6-day washout period. ECG, peripheral BP, and central BP measurements were obtained at baseline and 1, 2, 4, 6, and 24 hours post study drink consumption. The time-matched, baseline-adjusted changes were compared. The change in corrected QT interval from baseline in the energy drink arm was significantly higher than the caffeine arm at 2 hours (0.44±18.4 ms versus -10.4±14.8 ms, respectively; P=0.02). The QTc changes were not different at other time points. While both the energy drink and caffeine arms raised systolic BP in a similar fashion initially, the systolic BP was significantly higher at 6 hours when compared with the caffeine arm (4.72±4.67 mm Hg versus 0.83±6.09 mm Hg, respectively; P=0.01). Heart rate, diastolic BP, central systolic BP, and central diastolic BP showed no evidence of a difference between groups at any time point. Post energy drink, augmentation index was lower at 6 hours. The corrected QT interval and systolic BP were significantly higher post high-volume energy drink consumption when compared with caffeine alone. Larger clinical trials validating these findings and evaluation of noncaffeine ingredients within energy drinks are warranted. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02023723.

Energy Drinks and Their Acute Effects on Heart Rhythm and Electrocardiographic Time Intervals in Healthy Children and Teenagers: A Randomized Trial.

Journal: Cells

Authors: Guido Mandilaras, Pengzhu Li, Robert Dalla-Pozza, Nikolaus Alexander Haas, Felix Sebastian Oberhoffer

Publication Date: 2022-04-08

SHAPER's Take: This study reveals the adverse effects on heart rhythm in healthy children and teenagers after consuming energy drinks, an area previously not well-documented. This is crucial for understanding the specific cardiovascular implications of energy drinks, which are widely consumed globally by young populations. Highlighting energy drinks' ability to increase supraventricular extrasystoles, a type of heart arrhythmia, which indicates a disruption in normal electrical impulses. This might be primarily linked to the high levels of stimulants like caffeine, but other constituents such as taurine and sugar may also play roles. These findings emphasize the complex interplay of ingredients in energy drinks impacting cardiac rhythm.

Abstract: Beyond their effect on blood pressure, the effect of energy drinks on heart rate in children and teenagers has not been evaluated until now. Thus, this study aimed to investigate the acute cardiovascular effects of energy drinks in healthy children and teenagers. Twenty-six children and adolescents (mean age 14.49 years) received a commercially available energy drink (ED) and placebo on two consecutive days based on the maximum caffeine dosage as proposed by the European Food Safety Authority. Heart rhythm and electrocardiographic time intervals were assessed in a prospective, randomized, double-blind, placebo-controlled, crossover clinical study design. ED consumption resulted in a significantly increased number of supraventricular extrasystoles (SVES) compared to the placebo, whereas supraventricular tachycardia or malignant ventricular arrhythmias were not observed. The mean heart rate (HR) was significantly lower following consumption of EDs. In contrast, QTc intervals were not affected by EDs. Being the first of its kind, this trial demonstrates the cardiovascular and rhythmological effects of EDs in minors. Interestingly, EDs were associated with adverse effects on heart rhythm. Whether higher dosages or consumption in children with preexisting conditions may cause potentially harmful disorders was beyond the scope of this pilot study and remains to be determined in future trials. Trial Registration Number (DRKS-ID): DRKS00027580.

Impact of energy drink versus coffee consumption on periodic repolarization dynamics: an interventional study.

Journal: European Journal Of Nutrition

Authors: Dominik Schüttler, Wolf-Stephan Rudi, Axel Bauer, Wolfgang Hamm, Stefan Brunner

Publication Date: 2022-07-15

SHAPER's Take: Schüttler et al.'s findings illuminate the differential impact of energy drinks compared to coffee, despite identical caffeine content, on cardiac electrophysiology, specifically on periodic repolarization dynamics (PRD) that serve as an marker of sympathetic activation of the heart. Unlike coffee, energy drinks significantly elevate PRD levels, suggesting enhanced sympathetic cardiac activation, which may increase cardiac risk. This stresses the importance of looking beyond caffeine to other ingredients in energy drinks that may drive this effect. Along with the other studies mentioned above, you can see that the evidence that energy drinks can change your heart rhythm seem quite well supported.

Abstract: Caffeinated beverages are consumed daily throughout the world. Caffeine consumption has been linked to dysfunction of the autonomic nervous system. However, the exact effects are still insufficiently understood. Sixteen healthy individuals were included in the present non-randomized cross-over interventional study. All study subjects consumed a commercial energy drink (containing 240 mg caffeine), and in a second independent session coffee (containing 240 mg caffeine). High-resolution digital ECGs in Frank-lead configuration were recorded at baseline before consumption, and 45 min after consumption of the respective beverage. Using customized software, we assessed ECG-based biomarker periodic repolarization dynamics (PRD), which mirrors the effect of efferent cardiac sympathetic activity on the ventricular myocardium. The consumption of energy drinks resulted in an increase in PRD levels (3.64 vs. 5.85 deg²; p < 0.001). In contrast, coffee consumption did not alter PRD levels (3.47 vs 3.16 deg², p = 0.63). The heart rates remained unchanged both after coffee and after energy drink consumption. Spearman analysis showed no significant correlation between PRD changes and heart rate changes (R = 0.34, p = 0.31 for coffee, R = 0.31, p = 0.24 for energy drink). Our data suggests that sympathetic activation after consumption of caffeinated beverages is independent from caffeine and might be mediated by other substances. NCT04886869, 13 May 2021, retrospectively registered.

Electrocardiographic and blood pressure effects of energy drinks and Panax ginseng in healthy volunteers: A randomized clinical trial.

Journal: International Journal Of Cardiology

Authors: Sachin A Shah, Andrew Occiano, Tinh An Nguyen, Amanda Chan, Joseph C Sky, Mouchumi Bhattacharyya, Kate M O'Dell, Allen Shek, Nancy N Nguyen

Publication Date: 2017-08-11

SHAPER's Take: Shah et al.'s research elucidates the cardiovascular risks of consuming high volumes of energy drinks, highlighting significant increases in QTc interval and systolic blood pressure. This is particularly important as it dissects the mechanisms of cardiac risk associated with substances like caffeine and taurine in energy drinks, distinguishing them from other stimulants such as Panax ginseng, which demonstrated no significant effects on electrocardiographic or blood pressure parameters. Unlike the subtle cardiovascular impacts of coffee and other stimulants primarily attributed to caffeine, Shah et al.’s findings indicate that other ingredients in energy drinks may exacerbate cardiac risks, further fueling the controversy over their safety and the regulatory scrutiny they attract. While this study doesn’t identify which other ingredients are interacting so deleteriously with caffeine, it seems to rule out ginseng, which is helpful.

Abstract: Energy drink usage has been linked to emergency room visits and deaths. The objective of the study is to assess the electrocardiographic and blood pressure effects of energy drinks, Panax ginseng and placebo in healthy individuals. This was a randomized, double blinded, placebo controlled, crossover study. Young healthy volunteers with no comorbid conditions consumed 32oz of an energy drink, control drink with 800mg of Panax ginseng or matching placebo-control drink over 45min. Primary endpoints were QTc interval and systolic blood pressure. Secondary endpoints included QT interval, PR interval, QRS duration, heart rate, and diastolic blood pressure. All endpoints were assessed at baseline, 1, 2, 3.5, and 5.5h. A significant increase in QTc interval 2h post energy drink consumption was evident when compared to placebo (3.37±10.7ms and -3.19±11.8ms respectively; p=0.030). Similarly, systolic blood pressure 2h post energy drink consumption increased when compared to placebo (2.00±6.37mmHg and -2.67±5.83mmHg respectively; p=0.014). The PR interval significantly reduced over a 2h period post energy drink use in a clinically non-meaningful manner. Heart rate at 2h was not significantly higher in the energy drink group when compared to others. The QT interval, QRS interval and diastolic blood pressure were not impacted at any time point. Certain energy drinks consumed at a high volume significantly increase the QTc interval and systolic blood pressure by over 6ms and 4mmHg respectively. Panax ginseng does not have a significant impact on ECG or blood pressure parameters.

Energy-drink consumption is associated with asthma, allergic rhinitis, and atopic dermatitis in Korean adolescents.

Journal: European Journal Of Clinical Nutrition

Authors: Jee Hye Wee, Chanyang Min, Min Woo Park, Il-Seok Park, Bumjung Park, Hyo Geun Choi

Publication Date: 2021-08-11

SHAPER's Take: Wee et al.'s investigation find a surprising link between frequent energy drink consumption and increased rates of allergic diseases like asthma, allergic rhinitis, and atopic dermatitis among Korean adolescents. This finding is particularly intriguing because it suggests a broader systemic impact of energy drinks, beyond the commonly discussed cardiovascular and neurological effects. It’s always hard to separate out other variables like socioeconomic status and other health factors, but this study collected a lot of confounding variables and corrected for them.

Abstract: Few studies have evaluated the effects of energy drinks on allergic diseases. The purpose of this investigation was to evaluate the association between energy drinks and various allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis, in a large representative Korean adolescent population. This cross-sectional study used data from the Korea Youth Risk Behavior Web-based Survey collected from 2015 to 2016. A total of 129,809 participants (n = 67,056 for males; n = 62,753 for females) aged 12-18 years were included and were asked about their frequency of consumption of energy drinks such as Hot6^®, Redbull^®, and Bacchus^®. Their history of asthma, allergic rhinitis, and atopic dermatitis throughout life and in the last 12 months were obtained. The association between the frequency of energy-drink consumption and allergic diseases was analyzed using multiple logistic regression with adjustment for various covariates. Age, sex, physical activity, obesity, region of residence, economic level, paternal and maternal educational level, smoking, and alcohol consumption differed significantly according to the frequency of energy-drink consumption (each P < 0.001). Frequent energy-drink consumption (≥7 times a week) was significantly associated with asthma throughout life (odds ratio [OR] = 1.30, 95% confidence interval (CI) = 1.03-1.64, P = 0.025), asthma within the last 12 months (OR = 1.65, 95% CI = 1.16-2.35, P = 0.006), allergic rhinitis within the last 12 months (OR = 1.21, 95% CI = 1.02-1.44, P = 0.030), and atopic dermatitis within the last 12 months (OR = 1.49, 95% CI = 1.17-1.90, P = 0.001) compared to no energy-drink consumption in the full-adjusted model. Frequent energy-drink consumption is associated with allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis, in Korean adolescents.

Associations between adolescents' energy drink consumption frequency and several negative health indicators.

Journal: Bmc Public Health

Authors: Maija Puupponen, Jorma Tynjälä, Raili Välimaa, Leena Paakkari

Publication Date: 2023-02-08

SHAPER's Take: Puupponen et al.'s research underscores critical correlations between energy drink consumption among adolescents and broader adverse health effects and risky behaviors. This is one of the reasons that it’s hard to understand the effects of energy drink consumption - people who drink energy drinks are a lot more likely to have other bad habits that negatively effect their health.

Abstract: The purpose of this study was to identify how various negative health indicators are associated with energy drink consumption frequency among 13- and 15-year-old Finnish adolescents. Data (N = 2429) from the nationally representative international Health Behaviour in School-aged Children study (2018) were analyzed via descriptive analysis and logistic regression analyses, with control for salient covariates. Relative risks (RR) were derived from the adjusted odds ratios. Even infrequent energy drink consumption was associated with various negative health indicators. Moreover, as compared to non-users, frequent energy drink consumers were more likely to report several health-compromising behaviors: current smoking (RR = 9.85, 95% CI: 5.68-16.02), current snus use (RR = 3.62, 95% CI: 1.80-6.85), cannabis use (RR = 3.42, 95% CI: 1.69-6.52), alcohol consumption (RR = 3.08, 95% CI: 2.49-3.71), problematic social media use (RR = 2.53, 95% CI:1.68-3.72), short sleep (RR = 2.12, 95% CI: 1.69-2.60), skipping breakfast (RR = 1.87, 95% CI: 1.51-2.29), drunkenness (RR = 1.59, 95% CI: 1.11-2.23), inadequate tooth brushing (RR = 1.28, 95% CI: 1.05-1.54). In addition, frequent energy drink consumption was associated with perceived negative health indicators: feelings of insufficient sleep (RR = 1.56, 95% CI: 1.11-2.15), low self-rated health (RR = 1.48, 95% CI: 1.15-1.87), and multiple health complaints (RR = 1.31, 95% CI: 1.07-1.56). Energy drink consumption, even infrequent, was associated with several negative health indicators, and the reporting of these increased with the frequency of energy drink consumption. The findings support the concerns of health authorities regarding the negative associations between energy drink consumption and health, even among persons as young as 13 years. There is evidence to support specific policy level actions, including restrictions on the sale of energy drinks to adolescents. This measure has been proposed in a Finnish government program, but implementation has yet to occur. Moreover, marketing of these beverages in platforms that are popular among adolescents (e.g., the social media) should be rigorously evaluated, and comprehensive interventions and actions implemented to ensure that adolescents, parents/guardians, and professionals working with adolescents (e.g., in schools) have a good understanding of the links between energy drink consumption and health.

Why is everyone talking about microplastics?

Consumer Reports tested popular foods for phthalates - a plastic additive that has been found in strikingly high quantities in many packaged and fast foods, including those purporting to be healthy. A couple of surprises were on the list. Notably the protein shakes made by Fairlife Organic, popular among Shaper editors and readers, had 20mg of phthalates per serving, Annie’s organic cheesy ravioli came in highest with 54mg per serving, and Chipotle chicken burritos had 21mg per serving.

Another article that hit the mainstream, this time by NPR, brought attention to a study showing microplastics present in 100% of the adult male cohort’s testes. The study (with 23 human participants) built on an earlier study (with only 6 participants) to show that more widespread testing should be pursued.

There’s been a ton of research on this over the past few years, showing significant potential health risks associated with regular exposure. Research consistently shows that phthalates disrupt endocrine functions, impacting reproductive health, hormonal balance, and development. Elevated phthalate levels have been linked to reduced fertility, decreased male hormone synthesis, and adverse effects on fetal and child development - including increased risks of preterm birth and cardio-metabolic issues. Phthalate exposure has also been associated with deleterious effects in organ systems ranging from the heart to the liver. The overall body of evidence supports the conclusion that phthalates pose health risks, but ongoing research continues to refine our understanding of these risks. One interesting focus here is on how widespread these chemicals are. They are found in food, human subjects, institutional buildings, and even nail salons. We’ve dug in and found the best and latest research on the subject.

The Research

Below we summarize some of the critically important and representative papers on microplastics over the last few years, with a particular focus on phthalates. Among human study cohorts they have been shown to have a serious impact on reproductive health and infertility, metabolic and oxidative stress, cancer risk, cardiovascular health, the immune system (including children’s asthma), and neurodevelopment. Exposure risks extend from more controllable areas such as consumption of packaged food to less controllable areas such as environmental and household dust. Moreover, the impacts seems to be more pronounced in children. While most research on these effects in human subjects are more recent, people have noticed the link between plasticizers and hormones/fertility in male rats since the late 1980s. Thirty-five years of results make it less likely that human results shown are a result of p-hacking or similar statistical legerdemain. With half of the world’s plastics produced in the last 15 years we are just beginning to feel the impact on chronic disease and lifespan.

Associations of environmental phthalate exposure with male steroid hormone synthesis and metabolism: An integrated epidemiology and toxicology study.

Journal: Journal Of Hazardous Materials

Authors: Meiping Tian, Shuangshan Wu, Yi-Xin Wang, Liangpo Liu, Jie Zhang, Heqing Shen, Yanyang Lu, Huaqiong Bao, Qingyu Huang

Publication Date: 2022-08-15

SHAPER's Take: This study investigates the negative impact of phthalate exposure on male hormonal balance, which affects reproductive health and overall wellbeing. Hormone synthesis is one of the largest concerns for people worried about these chemicals, and this is one of the more thorough papers we could find on the topic.

Abstract: Humans are simultaneously and constantly exposed to various lipophilic chain phthalate acid esters. The association of urinary phthalate metabolites with altered male steroid hormone synthesis and metabolism was examined using epidemiology and toxicology studies. We measured 8 phthalate metabolites [monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), mono-n-octylphthalate (MOP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono (2-ethyl-5-oxohexyl) phthalate (MEOHP)] and two sex hormones [testosterone (T) and estradiol (E₂)] in single serum and repeated spot urine samples among 451 reproductive-age males. Moreover, in vitro experiments with Leydig cell MLTC-1 steroidogenesis and liver cell HepG2 efflux in response to mixed and individual phthalates were designed to simulate real-world scenarios of human exposure. As a joint mixture, the phthalate metabolite was inversely associated with serum T and E₂ concentrations but positively associated with urinary T and E₂ concentrations. Combined with in vitro experiments, DEHP metabolites were identified as the predominant contributor to the decline in hormone synthesis, and ATP-binding cassette (ABC) gene activation might be involved in hormone excretion. Exposure to environmentally relevant phthalates was associated with both altered steroid synthesis and excretion, which provides additional insights into the endocrine-disrupting potential of phthalates.

Paternal exposures to environmental chemicals and time-to-pregnancy: overview of results from the LIFE study.

Journal: Andrology

Authors: G M Buck Louis, D B Barr, K Kannan, Z Chen, S Kim, R Sundaram

Publication Date: 2016-07-04

SHAPER's Take: The online discourse on microplastics has focused on the “xenoestrogen” effect in men. This is one of the studies that shows this, concentrating on potential reduced fertility in men, emphasizing the often underestimated role of paternal health in reproductive success. By identifying specific chemicals that reduce fecundity, including phthalates, this research offers insight for people concerned about these effects as well as public health initiatives aimed at improving reproductive health outcomes (potentially including regulations on harmful environmental exposures)

Abstract: Published findings from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study regarding the relation between environmental chemicals and couple fecundity, as measured by time-to-pregnancy (TTP), are reviewed with a particular focus on role of the male partner. The LIFE Study recruited 501 couples from 16 counties in two U.S. states upon discontinuing contraception for purposes of becoming pregnant. Upon enrollment, couples provided a blood and urine sample for the quantification of persistent and non-persistent environmental chemicals, respectively, and then completed daily journals until pregnant or up to one year of trying. Female partners used fertility monitors to aid the timing of intercourse relative to ovulation, and digital home pregnancy test kits on the day of expected menses. Chemical classes included: metals, persistent organic pollutants, environmental phenols, and phthalates that were quantified using inductively coupled plasma mass spectrometry or isotope dilution high-resolution or tandem mass spectrometry. Time-to-pregnancy (TTP) was defined as the number of prospectively observed menstrual cycles required for pregnancy. Fecundability odds ratios (FORs) and 95% confidence intervals (CIs) were estimated for each chemical and partner after adjusting for potential confounders and accounting for right censoring and time off contraception. FORs < 1 are suggestive of diminished fecundity or a longer TTP. Significant reductions (ranging from 17-31%) in couple fecundity were observed for male partners' concentration of lead (0.83; 0.70, 0.98), 2,2',4,4'-tetrahydroxybenzophenone (0.69; 0.49, 0.97), monobenzyl (0.80; 0.67, 0.97), and monomethyl (0.81; 0.70, 0.94) phthalates after adjusting for the female partners' concentrations. Seven PCB congeners quantified in men's serum were associated with a 17-29% reduction in couple fecundity. Our findings underscore the importance of a couple-based exposure design, inclusive of the male partner, when assessing couple-dependent outcomes such as TTP to avoid misinterpretation of results based only upon the female partner.

Update about the disrupting-effects of phthalates on the human reproductive system.

Journal: Molecular Reproduction And Development

Authors: Inês Mesquita, Margarida Lorigo, Elisa Cairrao

Publication Date: 2021-10-06

SHAPER's Take: This is a great review of papers related to phthalates impact on reproductive health for both men and women, including infertility risks in men - a good starting point for people that want to get caught up on how phthalates disrupt the endocrine and reproductive system.

Abstract: Phthalate esters are synthetic chemicals used in the plastic industry as plasticizers and consumable products. According to United Nations, about 400 million tons of plastic are produced every year. In parallel with increased production, the concerns about its effects on human health have increased because phthalates are endocrine-disrupting compounds. Humans are continuously exposed to phthalates through different routes of exposure. Experimental data have associated phthalate exposure to adverse effects on development and reproduction in women (e.g., earlier puberty, primary ovarian insufficiency, endometriosis, preterm birth, or in vitro fertilization) and men (e.g., anogenital distance, cryptorchidism, hypospadias, and changes in adult reproductive function) although there is no consensus. Therefore, one question arises: could the increase in infertility be related to phthalate exposure? To answer this question, we aimed to assess the disrupting-effects of phthalates on the human reproductive system. For this, we reviewed the current literature based on epidemiological and experimental data and experimental studies in humans. The phthalate effects were discussed in a separate mode for female and male reproductive systems. In summary, phthalates induce toxicity in the reproductive system and human development. The increased plastic production may be related to the increase in human infertility.

Effects of phthalates on normal human breast cells co-cultured with different fibroblasts.

Journal: Plos One

Authors: Fang-Ping Chen, Mei-Hua Chien, Huang-Yang Chen, Yuet-Tong Ng

Publication Date: 2018-06-25

SHAPER's Take: Many people focus on the hormonal effects of phthalates on male infertility and testosterone levels, but they likewise seem to have an outsized effect on cancer risk for women. The study shows the potential endocrine-disruptive effects of phthalates on breast cell proliferation, particularly their capacity to behave similarly to estrogen. This paper suggests that even at low concentrations, phthalates could contribute to breast cancer development by influencing hormonal activities and cellular interactions in mammary tissues.

Abstract: Whether or not phthalates play a role in breast carcinogenesis remains to be determined. The goal of this study was to explore the effects of phthalates on the growth of normal MCF-10A breast cells modulated by breast fibroblasts. Fibroblasts were derived from normal mammary tissue adjacent to both estrogen receptor (ER) positive and negative primary breast cancers, which were grown separately from nontumorigenic MCF-10A epithelial cells. MCF-10A co-culture cells were treated with 10 nM 17β-estradiol (E2), Butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), and di(20ethylhexyl) phthalate (DEHP) (10 and 100 nM). After incubation for 120 hours, the cells were harvested and extracted for MTT assay. Western blot analysis was used to evaluate the proliferative pathway proteins and the effects on ER α. Only fibroblasts from ER (+) breast cancer significantly stimulated proliferation of MCF-10A cells. Exposure of the co-culture to E2, BBP, DBP, DEHP, and E2 combined with one of these phthalates resulted in significantly increased cell proliferation, as well as proliferating cell nuclear antigen (PCNA) and ER α expressions. The present study demonstrates that phthalates express a significant influence in fibroblast-epithelial interactions, similarly to the effects of E2 on breast cells. The effects of phthalates on normal breast cells depend upon ER modulating actions. In breast carcinogenesis, phthalates should be considered as having endocrine disrupting potential, even at low concentrations.

Phthalate Exposure and Coronary Heart Disease: Possible Implications of Oxidative Stress and Altered miRNA Expression.

Journal: Chemical Research In Toxicology

Authors: Asmaa Mohammad Moawad, Sara Awady, Abla Abd El Rahman Ali, Marwa Abdelgwad, Soliman Belal, Sarah Hamed N Taha, Marwa Issak Mohamed, Fatma Mohamed Hassan

Publication Date: 2024-05-20

SHAPER's Take: Moawad et al.'s research highlights the link between phthalate exposure and increased risk of coronary heart disease, suggesting oxidative stress and changes in miRNA expression as underlying mechanisms. This finding is crucial as it points to the potential for specific biomarkers for early detection and possibly an opportunity for targeted interventions to mitigate this risk.

Abstract: The relationship between phthalate exposure and coronary heart disease (CHD) is still unclear. This study aimed to investigate the association between phthalate exposure and CHD and determine the possible atherogenic mechanisms of phthalates by assessing oxidative stress and altering miRNA expression. This case-control study included 110 participants (55 CHD patients and 55 healthy controls). The levels of oxidative stress markers, malondialdehyde (MDA), and superoxide dismutase (SOD), and the expression of miRNA-155 (miR-155) and miRNA-208a (miR-208a), were measured and correlated with the urinary mono-2-ethylhexyl phthalate (MEHP). Highly significant differences were detected between the CHD cases and the control group regarding MEHP, MDA, SOD, miR-155, and miR-208a (p-value < 0.001). Spearman correlations revealed a significant positive correlation between MDA and MEHP in urine (P = 0.001 and rs = 0.316) and a significant negative correlation between SOD and MEHP in urine (P < 0.001 and rs = -0.345). Furthermore, significant positive correlations were observed between miR-155 and urinary MEHP (P = 0.001 and rs = 0.318) and miR-208a and urinary MEHP (P < 0.001 and rs = -0.352). This study revealed an association between phthalate exposure, as indicated by urinary MEHP and CHD; altered expression of miR-155 and miR-208a and oxidative stress could be the fundamental mechanisms.

Relationship between phthalates exposures and metabolic dysfunction-associated fatty liver disease in United States adults.

Journal: Plos One

Authors: Junhao Sun, Siqi Yang, Yue Zhang, Wenzhi Xiang, Xiubo Jiang

Publication Date: 2024-04-22

SHAPER's Take: Sun et al. reveal potential health risks linked to phthalates, common chemicals found in many everyday products, by demonstrating their association with increased risk of fatty liver disease tied to metabolic dysfunction in adults. This connection is especially concerning given the widespread use of phthalates and the rising prevalence of metabolic disorders. Their findings prompt reconsideration of phthalate exposure in everyday consumer products, emphasizing the need for further research and potential regulatory review.

Abstract: As a new definition for the evidence of hepatic steatosis and metabolic dysfunctions, the relationship between phthalates (PAEs) and metabolic dysfunction-associated fatty liver disease (MAFLD) remains virtually unexplored. This study included 3,137 adults from the National Health and Nutrition Examination Survey spanning 2007-2018. The diagnosis of MAFLD depended on the US Fatty Liver Index (US FLI) and evidence of metabolic dysregulation. Eleven metabolites of PAEs were included in the study. Poisson regression, restricted cubic spline (RCS), and weighted quantile sum (WQS) regression were used to assess the associations between phthalate metabolites and MAFLD. After adjusting for potential confounders, Poisson regression analysis showed that mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-n-butyl phthalate, mono-(3-carboxypropyl) phthalate, mono-ethyl phthalate (MEP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate were generally significant positively associated with MAFLD (P<0.05). Furthermore, the WQS index constructed for the eleven phthalates was significantly related to MAFLD (OR:1.43; 95%CI: 1.20, 1.70), MEHHP (33.30%), MEP (20.84%), MECPP (15.43%), and mono-isobutyl phthalate (11.78%) contributing the most. This study suggests that exposure to phthalates, individually or in combination, may be associated with an increased risk of MAFLD.

Combined effects of prenatal phthalate exposure on cardiometabolic risk score among 4- to 7-year-old children: MABC study.

Journal: Chemosphere

Authors: Hui Gao, Meng-Long Geng, Juan Tong, Bao-Lin Wang, Kun Huang, Yi Zhang, Hong Gan, Bei-Bei Zhu, Peng Ding, Qu-Nan Wang, Jian-Qing Wang, Cheng Zhang, Peng Zhu, Fang-Biao Tao

Publication Date: 2023-01-01

SHAPER's Take: It’s shocking to see the variety of different negative health effects that have been reproducibly linked to phthalates across women, men, and children. This study digs into the effects on children and how different timings and types of prenatal phthalate exposure can distinctly influence cardiometabolic health in early childhood. Understanding these associations helps in developing targeted interventions to improve cardiometabolic health outcomes from a young age, thereby reducing the risk of related diseases later in life.

Abstract: There is currently no consensus about the impact of prenatal phthalate exposure on blood pressure and glycolipids in children. Few studies consider the health effects as an integrated indicator. The combined effect of multiple phthalate exposures is often ignored. Based on the Ma'anshan Birth Cohort, 2298 woman-child pairs were included in this study. Maternal urine was collected in each trimester to analyze 6 phthalate metabolites. The overall cardiometabolic risk (CMR) score was calculated based on serum glycolipids and blood pressure for children aged 4-7 years. A higher score represents a less favorable CMR profile. The restricted cubic spline model was used to explore the relationship between prenatal phthalate exposure and childhood CMR score. In addition, the quantile g-computation and the Bayesian kernel machine regression were used to evaluate the combined effect. The MBP exposure in the 1st trimester (MBP-1st) and the MEP-2nd were non-linearly associated with the CMR score (F_nonlinear = 3.28 and 5.60, P_nonlinear = 0.0378 and 0.0038, respectively). The MBP-3rd (F_linear = 5.31, P_linear = 0.0012) and the ∑LMWP-3rd (F_linear = 4.37, P_linear = 0.0045) were negatively associated with the score in a linear manner. The phthalate mixture in the 2nd trimester increased the score (psil = 0.1747, 95% CI = 0.0077-0.3416), with the MEP being the most common [weights = 0.5290; posterior inclusion probability (PIP) = 0.40]. The phthalate mixture in the 3rd trimester decreased the score (psil = -0.2024, 95% CI = -0.4097－0.0048), with the MEHP (weights = -0.5101; PIP = 0.14) and the MBP (weights = -0.3993, PIP = 1.00) being the greatest contributors. In conclusion, the MBP-1st and the MEP-2nd are non-linearly associated with the cardiometabolic risk in children. The MBP-3rd and the ∑LMWP-3rd decrease the childhood risk. The combined exposure to phthalate mixture in the second and third trimester elevates and decreases the risk of childhood cardiometabolism, respectively.

Modulation of fetoplacental growth, development and reproductive function by endocrine disrupters.

Journal: Frontiers In Endocrinology

Authors: Sanjay Basak, Saikanth Varma, Asim K Duttaroy

Publication Date: 2023-10-03

SHAPER's Take: Basak et al.'s research underscores the potential health risks associated with prenatal exposure to common chemicals like bisphenols and phthalates. It highlights how these substances can alter fetoplacental development and have long-term effects on the metabolic and reproductive functions of the offspring. The study is particularly compelling as it connects everyday chemical exposure to critical changes in hormonal and developmental processes during pregnancy.

Abstract: Maternal endocrine homeostasis is vital to a successful pregnancy, regulated by several hormones such as human chorionic gonadotropin, estrogen, leptin, glucocorticoid, insulin, prostaglandin, and others. Endocrine stress during pregnancy can modulate nutrient availability from mother to fetus, alter fetoplacental growth and reproductive functions. Endocrine disrupters such as bisphenols (BPs) and phthalates are exposed in our daily life's highest volume. Therefore, they are extensively scrutinized for their effects on metabolism, steroidogenesis, insulin signaling, and inflammation involving obesity, diabetes, and the reproductive system. BPs have their structural similarity to 17-β estradiol and their ability to bind as an agonist or antagonist to estrogen receptors to elicit an adverse response to the function of the endocrine and reproductive system. While adults can negate the adverse effects of these endocrine-disrupting chemicals (EDCs), fetuses do not equip themselves with enzymatic machinery to catabolize their conjugates. Therefore, EDC exposure makes the fetoplacental developmental window vulnerable to programming in utero. On the one hand prenatal BPs and phthalates exposure can impair the structure and function of the ovary and uterus, resulting in placental vascular defects, inappropriate placental expression of angiogenic growth factors due to altered hypothalamic response, expression of nutrient transporters, and epigenetic changes associated with maternal endocrine stress. On the other, their exposure during pregnancy can affect the offspring's metabolic, endocrine and reproductive functions by altering fetoplacental programming. This review highlights the latest development in maternal metabolic and endocrine modulations from exposure to estrogenic mimic chemicals on subcellular and transgenerational changes in placental development and its effects on fetal growth, size, and metabolic & reproductive functions.

Prenatal exposure to phthalates and neurocognitive development in children at two years of age.

Journal: Environment International

Authors: Xi Qian, Jiufeng Li, Shunqing Xu, Yanjian Wan, Yuanyuan Li, Yangqian Jiang, Hongzhi Zhao, Yanqiu Zhou, Jiaqiang Liao, Hongxiu Liu, Xiaojie Sun, Wenyu Liu, Yang Peng, Chen Hu, Bin Zhang, Shi Lu, Zongwei Cai, Wei Xia

Publication Date: 2019-10-01

SHAPER's Take: Qian et al.'s research highlights the potential negative impacts of prenatal exposure to phthalates on children's psychomotor development, particularly regarding lower molecular weight phthalates. This shows a particular risk related to dietary consumption of phthalates during pregnancy, as they enter the fetal bloodstream.

Abstract: Phthalates are a family of endocrine disruptors with short elimination half-lives in the human body. To date, few epidemiological studies have examined repeated measures of maternal urinary phthalates and the combined effects of prenatal exposure to multiple phthalates on children's neurocognitive development. We aimed to investigate the association between children's neurocognitive development at 2 years of age and prenatal phthalate exposure, as assessed by repeated measurements during pregnancy, and to further examine the effects of co-exposure to multiple phthalates using cumulative risk assessment. Within a prenatal cohort in Wuhan, China, we measured five high-molecular-weight (HMW) phthalates and three low-molecular-weight (LMW) phthalate metabolites' concentrations in three urine samples collected in the 1st, 2nd, and 3rd trimester of pregnancy from each mother. We assessed neurocognitive development by Bayley Scales of Infant and Toddler Development (BSID) at 2 years of age (n = 476) to obtain the children's mental development index (MDI) and psychomotor development index (PDI). Higher exposure levels to LMW phthalates compared to HMW phthalates were observed in our population. Ln-transformed averaged concentration of mono-n-butyl phthalate (MnBP), a metabolite of the LMW phthalate di-n-butyl phthalate (DnBP) during pregnancy, was associated with decreased PDI scores in all children (β = -1.90, 95% CI: -3.43, -0.37). Similarly, the averaged sum concentration of ∑dibutyl phthalate (∑DBP) was associated with decreased PDI scores in all children (β = -1.89, 95% CI: -3.63, -0.15). A negative trend of association between exposure to HMW phthalates and PDI scores was observed in girls, while a positive association was found in boys. In cumulative risk assessment analyses, we consistently observed that the hazard quotient of DnBP (the parent compound of MnBP) was inversely associated with PDI scores in all children, whereas the hazard quotient of di-2-ethylhexyl phthalate (DEHP), an HMW phthalate, was positively associated with PDI scores in boys only. This study is the first to use repeated measurement of maternal urinary phthalates in all three trimesters to assess prenatal exposure in relation to children's neurodevelopment. Our study suggested a negative association between prenatal exposure to MnBP and children's psychomotor development, and potentially sex-specific associations between HMW phthalates and neurocognitive development among boys and girls. These findings warrant further confirmation.

Human Erythrocytes Exposed to Phthalates and Their Metabolites Alter Antioxidant Enzyme Activity and Hemoglobin Oxidation.

Journal: International Journal Of Molecular Sciences

Authors: Paulina Sicińska, Kinga Kik, Bożena Bukowska

Publication Date: 2020-06-24

SHAPER's Take: Sicińska et al.'s research reveals the potential health risks associated with phthalate exposure by demonstrating how these chemicals disrupt the redox balance in human erythrocytes (red blood cells). This imbalance, evidenced by altered antioxidant enzyme activity and increased hemoglobin oxidation, leads to the premature removal of these red blood cells from circulation, potentially leading to anemia, hypoxia, and cardiovascular disease.

Abstract: Phthalates used as plasticizers have become a part of human life because of their important role in various industries. Human exposure to these compounds is unavoidable, and therefore their mechanisms of toxicity should be investigated. Due to their structure and function, human erythrocytes are increasingly used as a cell model for testing the in vitro toxicity of various xenobiotics. Therefore, the purpose of our study was to assess the effect of selected phthalates on methemoglobin (metHb), reactive oxygen species (ROS) including hydroxyl radical levels, as well as the activity of antioxidative enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), in human erythrocytes. Erythrocytes were incubated with di-n-butyl phthalate (DBP), butylbenzyl phthalate (BBP), and their metabolites, i.e., mono-n-butyl phthalate (MBP) and monobenzyl phthalate (MBzP), at concentrations ranging from 0.5 to 100 µg/mL for 6 or 24 h. This study shows that the analyzed phthalates disturbed the redox balance in human erythrocytes. DBP and BBP, at much lower concentrations than their metabolites, caused a statistically significant increase of metHb and ROS, including hydroxyl radical levels, and changed the activity of antioxidant enzymes. The studied phthalates disturbed the redox balance in human erythrocytes, which may contribute to the accelerated removal of these cells from the circulation.

Phthalates in House and Dormitory Dust: Occurrence, Human Exposure and Risk Assessment.

Journal: Bulletin Of Environmental Contamination And Toxicology

Authors: Shen Xu, Chao Li

Publication Date: 2021-02-18

SHAPER's Take: Xu et al.'s research highlights the significant presence of phthalates in indoor environments. The study reveals that especially vulnerable groups such as infants, toddlers, children, and teenagers are at notable risk of DEHP exposure, surpassing safety thresholds. This brings attention to the need for stricter regulations and mitigation measures to protect these sensitive populations from potential health hazards associated with phthalate pollution in everyday living spaces.

Abstract: Phthalates are one of ubiquitous contaminants in the indoor environment. In this study, we analyzed concentrations and profiles of 9 phthalates in dust samples collected from houses and university dormitories in Nanjing, China. The total concentrations of phthalates in house and dormitory dust ranged from 111.4 to 3599.1 µg/g and 86.1 to 1262.3 µg/g, respectively. Phthalates in house was significantly higher than that in dormitory dust (p < 0.01). Di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and di-isobutyl phthalate (DiBP) were the three predominant compounds and accounted for more than 98% of total phthalates in the two microenvironments. The estimated daily intake (EDI) of phthalates, carcinogenic risk (CR) of DEHP, and hazard index (HI) values of DEHP, DBP and DiBP were estimated. Except for adults, the CR of DEHP for four subgroups (infants, toddlers, children, and teenagers) had exceeded the limitation, implying that they are at the risk of exposure to DEHP through dust ingestion.

Associations between Children's asthma and allergic symptoms and phthalates in dust in metropolitan Tianjin, China.

Journal: Chemosphere

Authors: Changqi Zhu, Yuexia Sun, Yuxuan Zhao, Jing Hou, Qingnan Zhang, Pan Wang

Publication Date: 2022-09-01

SHAPER's Take: Zhu et al. demonstrate that higher phthalate levels in household dust correlate with increased asthma and allergic symptoms in children, highlighting potential health risks from everyday exposure to these chemicals. Their findings are particularly compelling as they establish a dose-response relationship between diisobutyl phthalate concentrations and asthma, suggesting that reducing phthalate exposure in homes could mitigate some respiratory issues in children.

Abstract: Prevalences of allergies and asthma have increased through the past few decades around the world, especially in countries and regions that have adopted modern lifestyles. Epidemiological studies outside of China have found a relationship between phthalates concentrations in indoor dust and symptoms of respiratory, skin and nose allergies. The aim of our study is to investigate the association between children's asthma and allergic symptoms and concentrations of different phthalates in settled dust samples collected from children's homes in metropolitan Tianjin (Tianjin and Cangzhou), China. We selected 126 cases with current allergic symptoms and 254 controls without allergic symptoms from the cohort of 7865 children. We collected dust samples from children's bedroom and analyzed them for their content of diethyl phthalate (DEP), diisobutyl phthalate (DiBP), di-n-butyl phthalate (DnBP), butylbenzyl phthalate (BBzP), di-2-ethylhexyl phthalate (DEHP) and diisononyl phthalate (DiNP). We found a higher concentration of DEP in rhinitis children's homes (0.33 vs. 0.27 μg/g dust) and a higher concentration of DiBP in asthma children's homes (29.04 vs. 15.66 μg/g dust). The concentration of DiBP was significantly associated with diagnosed asthma (adjusted odds ratio (AOR): 1.30; 95% confidence interval (CI): 1.07, 1.57). A dose-response relationship was found between concentrations of DiBP in dust and asthma. This study shows that some phthalates are associated with allergic and asthma symptoms in children.

Effects of co-administration of Di(2-ethylhexyl)phthalate and testosterone on several parameters in the testis and pharmacokinetics of its mono-de-esterified metabolite

Journal: Toxicology

Author: Shinshi Oishi

Publication Date: 1989

SHAPER's Take: This is one of the first papers showing a strong effect of plasticizers on reproductive function in mammals. It’s from 1989! You’ll want to take this one with a grain of salt as studies in rats don’t consistently replicate in humans. One fun note - the paper has one author, unheard of for a medical paper today.

Abstract: The administration of 1 g/kg di(2-ethylhexyl) phthalate (DEHP) or 5 mg/kg testosterone for 1 week did not affect the testicular and prostatic gland weights in rats. However, co-administration of DEHP and testosterone induced severe testicular atrophy accompanied by a decrease of zinc concentration in the testis and reduction of the activity of testicular specific lactate dehydrogenase isozyme. These changes were similar to the results of high dose administration of DEHP alone. Values of biological half-life and area under the concentration-time curve (AUC) of mono(2-ethylhexyl)phthalate, the main metabolite of DEHP, in testes after a single co-administration of DEHP (p.o.) and testosterone (i.p.) were higher than those after DEHP administration alone. Resuits suggest that the co-administration of DEHP and testosterone enhanced the adverse effects of DEHP on testes as the result of changes in pharmacokinetic values of MEHP.

Our idea came about as we were discussing the widespread adoption of more deliberate and healthier living and how to improve our own health, longevity and quality-of-life. On one hand, traditional medical education focuses on normal physiology, pathophysiology, and the treatment of various pathologies that arise. However, almost no attention is given to how we can improve our normal physiology before serious consequences arise, beyond vague ideas like “eat better, exercise more”. As a result, most primary care physicians are uninformed on these topics. On the other hand, the amount of new and informative research being done to actually answer these questions is overwhelming. Searching pubmed for recent studies related to broad trends in men’s health, such as metabolic function, intermittent fasting, cold plunges, gut microbiome, and improving testosterone, we found over 2,000 new papers being published a week.

Combining our analytical and medical backgrounds, Shaper Health aims to deliver you data driven summaries of the most relevant and applicable research into your everyday health and wellness. We have created methods to sift through these mountains of new research, find the most compelling observational studies and randomized experiments on human cohorts, and then curate those based on our own expertise.

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