The next time someone tells you to take a walk — even if walking is not your favorite thing to do and you disagree — it’s probably the right move.
Recent research suggests that walking a little more often could help you add as much as 11 years to your life, depending on your activity level.
I’d say the Number You Won’t Forget: 11 Years … wouldn’t you agree?
For people who are not active, adding 30 to 45 minutes of walking per day can have a dramatic life-extending impact. And even if you’re already active, adding more movement can give you a boost, too.
If you increase your daily movement up to approximately 8,000 to 10,000 steps per day, the study suggests you could add anywhere from 2 to 5 more years to your life.
The connection between walking and lifespan might be a byproduct of how movement helps keep you healthier and protect against the most common forms of death.
In another study, scientists analyzed data from 196 peer-reviewed articles, including more than 30 million people.
They found that people who did at least 75 minutes of moderate-intensity exercise every week reduced their risk of premature death by nearly 25 percent. And that’s because they lowered their risk of cardiovascular disease (leading cause of death) and cancer.
Put another way, cranking up the intensity for about 11 minutes per day — such as sprinting up the stairs several times — could be all it takes to experience the benefits.
No matter how you approach exercise, the research is clear that it doesn’t matter what type of movement you prefer or even if you go to the gym. But it does matter that you move often and daily.
If you have any questions on how you can optimize your health and fitness, feel free to Contact Us and we will assist you in whatever way possible to accomplish your goals!
Contact us, a healthcare professional or highly skilled coach or personal trainer for personalized guidance.
Sample Workout Routine:
Day 1: Chest / Triceps
Day 2: Rest
Day 3: Back / Biceps
Day 4: Rest
Day 5: Legs / Shoulders
Day 6-7: Active recovery (e.g., walking, swimming)
We don’t list Abdominals in the above because we feel you can train them very well by pulling in your stomach muscles and tightening them during each of the above exercises. This will train them to be “sucked in” and this will give you that V-tapered look most bodybuilders strive for.
You can, of course, add some extra work to the abs if you feel it necessary.
Remember that building muscle takes time and effort. By following these steps and remaining consistent, you can achieve your muscle-building goals.
If you need assistance, feel free to contact us any time!
Is Creatine Bad for Your Kidneys? Here’s What The Science Says…
While this is an “anabolic” group usually dealing with things like steroids, sarms, prohormones and peptides, I feel it would be a dereliction of duty to not occasionally address what should be staples in the life of every bodybuilder and fitness enthusiast… and in this case I am talking about Creatine!
Creatine is anabolic… In a big way!
Creatine is a compound that comes from three amino acids. It is found mostly in your body’s muscles as well as in the brain. Most people get creatine through seafood and red meat — though at levels far below those found in synthetically made supplements.
Benefits of Creatine
Muscle gain
Brain function
Enhances brain function
Enhances muscle volumization
Exercise performance
Better athletic performance
Benefits strength
Blood sugar control
Many of you have asked about Creatine’s kidney safety. After all, it appears to be one of the biggest hesitations, and a new study tried to settle the debate once and for all.
Scientists used one of the most advanced forms of statistical analysis and found creatine supplementation does not harm kidney function.
Researchers conducted a Mendelian randomization analysis—a technique that minimizes confounding variables—to explore whether increased creatine levels have any causal effect on renal function. Instead of relying on traditional observational studies (which can be influenced by lifestyle factors), this method allowed scientists to examine markers associated with creatine metabolism and their relationship to kidney health.
Even when people used larger doses, there was no relationship between higher levels and kidney function. This supports previous clinical trials showing that supplementation does not harm kidney health in healthy individuals, even with long-term use.
However, if you have pre-existing kidney disease, it’s always best to consult your doctor before supplementing.
Creatine is experiencing a renaissance because of the overwhelming amount of research suggesting many potential health benefits. It’s not just that it can make you stronger or help you build muscle, but it might also improve brain health, fight against cognitive disorders, and even improve focus and attention when you’re sleep-deprived.
There are many versions of creatine, but monohydrate is, by far, the most tested and trusted form.
Even when people used larger doses, there was no relationship between higher levels and kidney function.
So, with all of the muscle building, strength and power increasing benefits you can derive from the use of Creatine… this suggests that NOT to use it is a huge disservice to yourself in the quest for muscle mass, stamina and strength.
If you’d like to know where to get a very high quality Creatine product, as well as Protein and other similar products… just send me a message and I’d be happy to share!
The latest health trend feels like a way to cut the excess and put your energy into the things that matter.
But it’s all a dangerous illusion.
Instead of cutting out the BS, you’re told you’re not doing enough, and more is the antidote.
The wellness industry is overflowing with fear-based recommendations designed to create knee-jerk reactions.
You’re so busy playing whack-a-mole to the threats lurking in every food and behavior that you don’t have the time to question if you’re really in danger or if the new changes you’re making are making you better.
❝ Most optimization programs give you a mop to clean up a spill without ever considering what caused the leak.
Meat is dangerous, but so are some vegetables. Seed oils are to blame for everything, even though some of the longest-living populations consume seed oils regularly. We blame “hormone imbalances,” and yet few people test their hormones or understand what a hormone imbalance would really do to your body. Some people say high-intensity exercise will raise cortisol too much, while others suggest that walking isn’t even exercise.
And yet, all of this is strangely familiar. The difference is that technology and social media cause you to consume all the conflicting, confusing information at an unsustainable and overwhelming pace.
The solution is “optimization.” But it’s missing the most important ingredients to help you unlock optimal health.
Most optimization programs give you a mop to clean up a spill without ever considering what caused the leak.
It’s almost too easy to convince you that you’re failing at health without considering your individual needs.
If you’re tired of reacting to everything, “the Kick Test” is something I’ve used for more than 20 years as a truth serum.
It’s based on the famous quote from Bruce Lee,
“I fear not the man who has practiced 10,000 kicks once, but I fear the man who has practiced one kick 10,000 times.”
The Kick Test helps you get closer to mastery by limiting what you’re doing to improve your health and helping you build bulletproof behaviors.
When it comes to health, more is not more. And complication is not a sign of effectiveness.
❝ If you want to be optimized, sometimes it helps to be minimized in the name of mastery.
Optimization has missed out on a glorious opportunity to minimize instead of maximize.
We celebrate 27-step morning routines and complex behaviors as the only way to improve your health.
But, as Arnold Schwarzenegger would say, “It’s all bogus.”
Complication might seem like the best way to leave no stone unturned, but it’s a distraction. Instead, it’s far better to focus on small behaviors with asymmetrical upside.
People are doing more and more, so they tend to become less efficient and effective. And it’s why many feel over-stressed and overwhelmed by their health plans.
The truth?
You don’t need more exercise variety. You need to be able to perform a few exercises incredibly well.You don’t need endless sets and reps. You need to push yourself with maximum intensity and chase the hard reps.You don’t need to eat all the super foods. You need to find a few nutrient-dense foods you can eat repeatedly and consistently.You don’t need a long morning or evening routine. You need to find something that helps you start and end the day in a way where you feel good — which is determined on an individual level, not some global ideal.You don’t need a complicated sleep routine. Find something that helps you wind down — even if it’s some form of entertainment — and let that set the stage to help you doze off into peaceful slumber. If you’ve done everything, you can look into other purchases that might help, but only if you’ve put time and energy into the basics.
The Kick Test is simple and invaluable because it helps you focus on “one kick” instead of 10,000. Here’s how it works:
The Kick Test
Step 1: Identify the problem(s) you’re experiencing with your health.
If you’re going to improve, you must honestly assess what is wrong.
Step 2: Determine what you are doing to fix those problems.
Make a list of what you’re doing to solve what you found in step 1. It might be nothing; it might be everything. Just be honest.
Step 3: Acknowledge why you have chosen those actions.
Is it based on a real test (you got blood work done or did a movement screen), or is it based on suggestion and manipulation? (An influencer told you that your hormones weren’t balanced in the absence of any real data)
Step 4: Ask yourself, “What is the one behavior I can consistently do that will also have the most upside?”
This is a two-part question. Consistency is the most important variable of success. But if you consistently do something that moves pebbles instead of boulders, you’re putting in a lot of effort for something that won’t have a significant impact. I’ve met many people who have punished themselves by fasting in the name of “autophagy” when they could’ve seen similar outcomes by just restricting daily calories or resistance training more frequently.
Step 5: Minimize, re-focus, and master
Once you have the one thing, your job is to turn that into a habit that feels automatic, and then measure if your life improves. Remember, mastery takes time. It’s not a day or a week. You might spend months mastering one habit and then add another.
You will be tempted to add more, but you don’t need 10,000 kicks. You need one kick you’ve practiced 10,000 times. I’ll give you a few examples of my “one kick.”
Diet: I don’t struggle with protein, but I do with fiber. So that’s been all I’ve focused on to help me manage hunger. Every meal has fiber. I also find ways that are easiest for me to squeeze in fiber. It can be a high-fiber wrap. A powder into a protein shake. Vegetables baked into meals. The idea is to find something I enjoy and then make fiber a part of what I like.
Exercise: Walking used to be my kryptonite. I did not move at all outside of the gym.. Now, I have a calendar reminder throughout the day that forces me to get up and move. It’s a non-negotiable. I make it work, first hitting an average of 7,000 daily steps three years ago, then 10,000 per day two years ago, and finally 11,000+ steps daily last year without a thought (And just five years ago, I averaged 3,000 steps per day).
Sleep: I didn’t realize it, but my late-night snacking affected my sleep. I don’t struggle with falling asleep, but I would wake up, and my sleep quality wasn’t as good. So I have hard rules (closed kitchen) about when I eat my last meal. I don’t over-stress or worry about anything else. I just try to be good about when I stop eating and drinking relative to when I sleep.
Are there more things I can do? Sure. But every additional effort or stress could have a cost, as well. So, I have to weigh my efforts vs. my outcomes, as well as what I want to accomplish.
I know my health goals and frustrations, and I understand that optimization isn’t about perfection; it’s about feeling better, performing well, and making sure I don’t have glaring weaknesses that hold me back.
If at any time I start to struggle, I do another kick test, see where I need to improve, identify where I’m wasting effort, and get back to leaning into mastery.
It rarely looks impressive. It won’t get clicks on social media. But it’s an incredibly effective way to deliver results and feel better without burning out or losing your mind. And that sounds pretty optimal to me.
Some people use biological age to determine how well you’re aging. Others use strength metrics like grip strength or pushups. But your bedroom activity might be another option.
New research suggests that frequent (safe) sex is associated with a lower risk of cardiovascular disease and all-cause mortality.
Scientists analyzed the health outcomes of more than 17,000 people over 11 years.
The research suggests that those who engage in sexual activity less than 12 times per year have the highest risk for cardiovascular disease.
While we can’t assume cause and effect, regular sexual activity is linked to several health benefits, including reduced stress, improved blood circulation, and better heart rate variability—all factors associated with cardiovascular health. Additionally (all jokes aside), sexual activity can be a form of physical exercise, helping to maintain a healthy weight and improve metabolic function.
A slow sex life could be a sign of another health issue. Low testosterone, which can reduce sex drive and activity, is associated with higher levels of cholesterol and inflammation, which can also lead to a higher risk of cardiovascular disease.
And it might not be about having the best sex life, but just making sure you have some sex life.
The protective effect was most noticeable in those engaging in sexual activity at least once a week.
However, there did not appear to be additional health benefits for those who had sex more than 100 times per year.
Tesamorelin, a growth hormone-releasing hormone analogue that will help you lose visceral fat, is approved for the treatment of central adiposity/lipohypertrophy. Indeed, compared to placebo, Tesamorelin significantly decreases Visceral Adipose Tissue and improves lipid profiles in 26–52 weeks of treatment. It can make SIGNIFICANT changes to your physique when given enough time to do so.
Will Tesamorelin help build muscle?
Compared to placebo, tesamorelin resulted in significantly greater increases in muscle density across all total muscle groups and in the lean anterolateral/abdominal and rectus muscle, even after adjusting for differences at baseline.
Does Tesamorelin help You Lose Visceral Fat?
In two Phase III clinical trials of patients with abdominal obesity, Tesamorelin selectively reduced Visceral Adipose Tissue area by 15% over 26 weeks without altering subcutaneous adipose tissue (SAT) or body mass index (BMI).
Is Tesamorelin anti-aging?
GH is needed for optimal bone density and strength, and it is effectively stimulated by Tesamorelin, which also offers some rejuvenating effects on skin that typically manifest as reductions in wrinkles and other age-related skin changes resulting from lower GH levels.
How do you prepare Tesamorelin?
Reconstitution. Reconstitute vial containing 2-mg of tesamorelin with 2 mL of sterile water for injection (ask manufacturer for this) to provide a solution containing 2 mg/2 mL.
When To Do Your Injections?
It is usually injected once a day. Take your injection at around the same time every day. Typically recommended to use right before bed time, at least 1 hour after the last food of the day. (preferably longer)
Tesamorelin Dosage
While there are many schools of thought on dosage, we believe a dose ranging anywhere between .25 mg per day (250mcg) to 1 mg per day is sufficient. You can experiment a bit with this to find what works best for you.
Can You Stack It?
Yes you certainly can! And the best peptides for doing that are:
RETATRUTIDE : probably the best single fat burning peptide available today utilizing a unique 3-pronged approach to burning fat.
TIRZEPATIDE : A superior fat burning peptide known for good results.
SEMAGLUTIDE : A champion in reducing hunger and promoting feelings of fullness.
AOD 9604: Targets fat cells directly to promote fat loss without affecting blood sugar levels.
ADIPOTIDE : Unique fat killing peptide that does not just burn fat… it actually “kills” fat cells. Stacks great with all other fat burners.
In Conclusion:
Tesamorelin is an excellent peptide to help you lose visceral fat. This being the most dangerous kind of fat, we feel this is important to lose as much of it as possible. Tesamorelin can help you do that!
If you have any questions concerning this peptide, or any other Steroid, Sarm or Peptide… feel free to ask our highly qualified Specialist and we will be happy to assist you!
Peptides help build muscle by increasing protein synthesis, releasing growth hormone, and repairing tissue. However, peptides for muscle growth are not a magic solution and should be used intelligently and responsibly. We encourage you to always seek out the guidance of a professional who has experience with the use of peptides for these purposes. We welcome your inquiries on this subject here! You should also maintain a healthy lifestyle with proper nutrition and exercise.
Some peptides that may help with muscle growth include:
Ipamorelin – Stimulates the pituitary gland to release growth hormone, which can promote muscle growth and reduce body fat.
BPC-157 – Made of amino acids, BPC-157 can help increase cell growth, reduce pain and inflammation, and burn fat.
CJC-1295 – A synthetic peptide that increases growth hormone-releasing hormone (GHRH) levels, which stimulates the pituitary gland to release more growth hormone.
Sermorelin – A synthetic peptide that stimulates growth hormone release, which can increase muscle mass, reduce body fat, and improve energy levels.
CJC 1295 and Ipamorelin – A combination of two peptides that work together to stimulate growth hormone release and promote protein synthesis.
IGF-1 – A peptide hormone that regulates the growth and development of muscle tissue.
MK-677 is yet another great peptide that can help build muscle!
There are others that are possible, plus you can also stack certain Steroids and Sarms with your peptides to arrive at the perfect cycle for your goals.
Do peptides actually work for muscle growth?
Peptides are chains of amino acids, while steroids are ring-shaped fatty molecules. Both can help you build muscle and burn body fat, but they do it through different processes.
Our Thoughts On the Subject
We feel that peptides are an effective and safer way to build muscle if you want to use an anabolic aide. And while they will not produce quite as many gains as most Steroids or Sarms… they do definitely work!
I would recommend to always get products that will cover the 3 basic needs for a complete and complimentary stack… those being: You should get a product to increase Testosterone, and another product that will boost HGH, and we also recommend another anabolic (most likely an oral) to round out the trio.
To recap, use a: Testosterone – HGH – Anabolic
We have found the best results typically result from following this basic formula, and of course, these recommendations can be tweaked and adjusted to suit YOUR individual needs!
If you’d like help in creating a plan that will work for you and your personal goals… feel free to CONTACT US for help. We will be more than happy to assist you to get on the right track to be sure you are getting what would be best for your goals!
Delta sleep-inducing peptide (DSIP) has many potential benefits, including:
Sleep: DSIP can help improve sleep quality, regulate sleep patterns, and reduce sleep disturbances.
Pain: DSIP can help reduce pain states in people with chronic pain, alcoholics, and opiate addicts.
Stress: DSIP can help relieve emotional and psychological responses to stress, and reduce oxidative stress.
Withdrawal syndrome: DSIP is being used in clinical trials to treat withdrawal syndrome from alcohol and opiates.
Hormone levels: DSIP can help improve hormone levels.
Physical performance: DSIP can help improve physical performance.
DSIP is a natural nonapeptide that’s found in the brain and easily passes the blood-brain barrier. It’s thought to influence sleep by affecting neurotransmitters and brain receptors involved in sleep regulation.
What does DSIP do?
DSIP is involved in neuroendocrine regulation and release of anterior pituitary hormones. In humans, DSIP influences the secretion of adrenocorticotropic hormone (ACTH), luteinizing hormone (LH) and growth hormone (GH). It also plays a role in the regulation of circadian rhythms.
What is the DSIP peptide growth hormone?
Since the peptide induces EEG changes characteristic of slow-wave sleep and since GH release is associated with this type of sleep in the human, it is possible that DSIP may be involved in mediating sleep-induced GH release.
PT-141, also known as bremelanotide, is an innovative new peptide hormone treatment that works for both men and women to improve sexual function. PT-141 is an effective and efficient treatment for both erectile dysfunction and increased libido in men and improves female sexual arousal in women. PT 141 peptide gives you the desire and motivation along with the ability to increase blood flow to the penis or vagina and clitoris, returning the intimacy and passion to your relationship……
PT-141 addresses those issues to help resolve sexual difficulties.
PT-141 works directly through the nervous system to increase arousal, desire, and satisfaction with sex. Treatments like Viagra and Cialis work through the vascular system and only give you the ability to achieve an erection. However, PT-141 gives you the desire and motivation along with the ability to achieve an erection, returning the intimacy and passion to your relationship.
When Can I Expect to See Results?
While patients will notice some significant increases changes in the body after the first month, the full-benefits are usually fully noticed after three to six months of therapy.
MONTH 1
Increased energy
Improved stamina
Deeper, more restful sleep
MONTH 2
Improved skin, reduced wrinkles
Stronger nails and hair
Increased metabolism
MONTH 3
Enhanced sex drive and performance
Improved mental focus
Improved joint health
MONTH 4
Continued weight reduction
Improved skin elasticity
Increased lean muscle mass
MONTH 5
Noticeably fuller and healthier hair
Reduced appearance of wrinkles, better skin tone
Continued reduction in belly fat
MONTH 6
5-10% reduction in body fat (without exercise/diet)
10% increase in lean muscle mass
Improved vitality due to organ regrowth
How Do I Take PT-141?
The easy subcutaneous self-injection of PT-141 is made just underneath your skin, and is only given once every 72 or more hours. It is often recommend that men or women dose with the medication once or twice per week at 1.25 mg per dose, or as needed, to enjoy having their desired libido and sexual function. It usually takes anywhere from 2 – 4 hours to take effect. Under the direct care of a physician your PT-141 dose will be titrated to meet your exact needs. The fact that you only need one injection every 72 or more hours allows for spontaneity. Many people who use oral medication for erectile dysfunction often comment on the fact that they have to take a pill and “wait” for it to take effect, sometimes to the chagrin of their sexual partner. With a every 72 hours or so dosing schedule PT-141 does not get in the way of spontaneity. At this twice per week dosing protocol, a 10 mg vial of PT-141 will last you a month.
Tirzepatide is a synthetic derivative of gastric inhibitory polypeptide (GIP) that has simultaneous glucagon-like peptide-1 (GLP-1) functionality as well. This combination allows Tirzepatide (Mounjaro) to lower blood glucose levels, increase insulin sensitivity, boost feelings of satiety, and accelerate weight loss.
Tirzepatide was developed to fight type 2 diabetes, but has additionally been shown to protect the cardiovascular system and act as a potent weight loss agent.
Benefits of Tirzepatide
Decreases blood sugar
Reduces hunger
Reduces body fat
Dosage Information
Doses start at the 2.5 mg dose once weekly; after 4 weeks on the 2.5 mg dose, increase to the 5 mg dose once weekly. If higher doses are required, increase by 2.5 mg increments after at least 4 weeks at the current dose. The maximum dose is 15 mg once weekly.
Tirzepatide
Tirzepatide is a synthetic analogue of gastric inhibitory polypeptide (GIP) that was developed for its ability to stimulate insulin release and thus address both type 2 diabetes and nonalcoholic fatty liver disease. Made up of 39 amino acids, the relatively large Tirzepatide (Mounjaro) stimulates the release of insulin from the pancreas by binding to both GIP and GLP-1 (glucagon-like peptide-1) receptors. Taken over longer periods of time, Tirzepatide increases adiponectin levels by as much as 26% as well[1]. Research shows that Tirzepatide reduces feelings of hunger, lowers insulin levels, and increases insulin sensitivity. Taken together, these effects cause significant weight loss of 11 kg (25 lbs), improve glucose tolerance, decrease fat (adipose) tissue, and reduce cardiovascular risk.
What Does It Do?
Tirzepatide increases the release of insulin from the pancreas resulting in improved glucose control. Research shows that, in individuals with Type 2 diabetes, Tirzepatide (Mounjaro) decreases hemoglobin A1c (HbA1c) levels by 2.4% after six months. The peptide also appears to aid in weight loss, showing a dose-dependent relationship and helping individuals lose as much as 11 kg (25 lbs) over six months.
It isn’t just that Tirzepatide increases insulin release though. Research suggests that the peptide actually improves the function of pancreatic beta cells, the cells that make and release insulin. Studies suggest that Tirzepatide may actually make beta cells more effective at processing insulin, which leads not just to increases in insulin levels in the bloodstream, but decreased stress on the beta cells themselves. This may, in turn, help to slow the progressive nature of type 2 diabetes.
Research shows that Tirzepatide doesn’t just increase insulin levels at random though it appears to do so only in response to increased blood glucose levels. During fasting, Tirzepatide actually decreases insulin levels and thus helps to increase insulin sensitivity over time. It also decreases fasting levels of glucagon, which are thought to exacerbate hyperglycemia by interfering with hepatic glucose metabolism. Overall, these changes are a big part of the reason Tirzepatide has a profound effect on glucose and, ultimately, HbA1c levels.
How Does It Work?
Tirzepatide is a dual agonist of the gastric inhibitory polypeptide receptor and the glucagonlike peptide-1 receptor. Action at these receptors appears to have synergistic effects that make Tirzepatide more effective than strict GLP-1 agonists that are already approved for the treatment of type 2 diabetes. The affinity of Tirzepatide for the GIP receptor is greater than its affinity for the GLP-1 receptor.
Gastric inhibitory polypeptide, which is also referred to as the glucose-dependent insulinotropic polypeptide, is synthesized naturally in the small intestine. This polypeptide binds to the GIP receptor to inhibit gastric acid secretion and gastrin release while stimulating insulin release. The latter is the primary function of GIP-R and is the primary reason that insulin levels increase following a meal.
Glucagon-like peptide-1 receptors are found on beta cells as well as in neurons in the brain. Like GIP-R, stimulation of GLP-1R stimulates the release of insulin. Natural agonists include glucagon and GLP1, but it has also been shown to bind nearly a dozen synthetic agonists including dulaglutide, lithium, and oxyntomodulin. Activation of GLP-1R increases both insulin synthesis and insulin release, factors that have made it a desirable target in drug development. In the brain, GLP-1R stimulation lowers appetite.
Interestingly, stimulation of GLP-1R appears to increase beta cell density in the pancreas. GLP-1R stimulation increases expression of the anti-apoptotic bcl-2 gene while reducing expression of pro-apoptotic bax and caspase-3 genes. This leads to enhanced beta cell survival and, ultimately, to increased levels of insulin.
The combination of GIPR and GLP-1R activity is what gives Tirzepatide an edge over strict GLP-1R agonists. Research shows that Tirzepatide acts identically to GIP at the GIPR, but favors cAMP production over β-arrestin recruitment when acting at the GLP-1R. These details may seem esoteric to some extent, but this difference in activity from endogenous GLP-1 appears to cause GLP-1R activation without increasing physiological internalization of the receptor. The net result is enhanced GLP-1R activity with Tarazepide compared to both endogenous GLP-1 as well as other synthetic GLP-1R agonists. These slight alterations mean that Tirzepatide drastically enhances insulin secretion, promotes feelings of satiety, and reduces inflammation in adipose tissue. These combined effects make it a highly efficacious anti-diabetes peptide.
Finally, Tirzepatide appears to alter adiponectin levels, raising overall levels of the fat-burning peptide. Increased levels of adiponectin reduce fat cell differentiation and increase energy expenditure by making mitochondria more inefficient. A low level of this peptide hormone has been implicated in diseases such as type 2 diabetes, atherosclerosis, and non-alcoholic fatty liver disease. It is worth noting that elevated adiponectin levels elevate insulin sensitivity, so it would appear that Tirzepatide modulates insulin sensitivity via several mechanisms.
Tirzepatide and Hunger
Research shows that Tirzepatide delays gastric emptying during the earliest phases of its administration but that the effect diminishes over time as a result of tachyphylaxis. These effects are similar to those seen with pure GLP-1R agonists, indicating that this action of Tirzepatide is almost completely controlled by its GLP-1 activity and not at all by its GIP activity. It appears that the effects of Tirzepatide on gastric emptying can be prolonged if the peptide is taken at a low dose for four weeks and then the dose is escalated. This also helps to mitigate side effects caused by the peptide and creates a veritable win-win for patients. Delayed gastric emptying can help to increase feelings of satiety and reduce hunger as well as food cravings. Combined with the effects Tirzepatide has on glucose levels, this can actually help to alter eating patterns over the long term.
Tirzepatide and Weight
As noted above, Tirzepatide use is associated with substantial weight loss over a six-month time interval. A comparison of Tirzepatide to other GLP-1 analogues, like degludoc, indicates a striking difference. Whereas Tirzepatide causes a dose-dependent decrease in weight over time, degludoc and other GLP-1R agonists cause weight gain.
It appears that the GIP agonism cause by Tirzepatide is what is responsible for the peptide’s long-term effects on weight. GIP appears to directly impact the insulin-sensitivity of adipocytes, which is likely the mechanism by which Tirzepatide impacts adiponectin levels. In short, Tirzepatide activates GIP receptors in fat cells, which then leads to an increase insulin sensitivity. This, in turn, leads to a reduction in adipose inflammation as well as an increase in adiponectin levels and the associated benefits. This isn’t the whole picture, however research shows that GIP signaling in the central nervous system regulates hypothalamic feeding centers leading to decreased food intake and improved glucose handling. This, in turn, leads to decreased body weight. Thus, it appears that Tirzepatide impacts weight via adiponectin signaling directly in adipose tissue and via CNS alterations that reduce hunger levels via GIPR signaling in the brain.
Tirzepatide and the Heart
As noted, Tirzepatide alters adiponectin levels. Low adiponectin has been associated with atherosclerosis, obesity, and heart disease while increased adiponectin levels have been associated with decrease risk of all of these things. Research in humans with type 2 diabetes has shown that Tirzepatide improves lipoprotein biomarkers, lowering levels of triglycerides, apoC-III, and a handful of other lipoproteins. Combined, these effects mean reduced risk of heart disease as a likely result of decreased adiposity. Research shows that increased adiponectin levels increase HDL levels while decreasing triglyceride levels, both of which are associated with lower risk of heart disease. The peptide hormone appears to go further though, reducing scavenger receptors in macrophages and increasing the levels of cholesterol efflux to greatly protect against atherosclerosis. Increases in adiponectin levels have been associated with improved nutrition, exercise, and the use of certain lipid-lowering medications. It appears that Tirzepatide has similar beneficial effects.
Research shows that GLP-1 is important in both the direct regulation of cardiovascular risk factors such as hypertension, dyslipidemia, and obesity as well as in the indirect regulation of risk factors like inflammation and endothelial cell dysfunction. The former effects are discussed above and below in relationship to adiponectin. The effects on inflammation and endothelial function, however, appear to be mediated more directly.
In the case of endothelial function, GLP-1 signaling has been shown to induce relaxation of blood vessels leading to decreased blood pressure and enhanced end organ perfusion. This effect appears to result from increased expression of eNOS, the enzyme that generates nitric oxide and induces vascular relaxation. Interestingly, these effects appear to be enhanced in the setting of preexisting cardiovasulcar disease and diabetes.
Of course, it is well known that inflammation is directly correlated with atherosclerosis. The details are still being worked out, but GLP-1 signaling appears to decrease inflammation via a handful of mechanisms including reduced NF-κB signaling, decreased MMP-9 activity, inhibited inflammatory cytokine synthesis, and decreases in inflammatory macrophage activity. What is more, these effects appear to last as long as three months after a single dose of a GLP-1R agonist like Tirzepatide. Tirzepatide is undergoing a clinical trial to further evaluate its medium-term effects on individuals with heart failure.
Summary
Tirzepatide is a synthetic derivative of gastric inhibitory polypeptide (GIP) that has simultaneous glucagon-like peptide-1 (GLP-1) functionality as well. This combination allows Tirzepatide to lower blood glucose levels, increase insulin sensitivity, boost feelings of satiety, and accelerate weight loss. Tirzepatide was developed to fight type 2 diabetes, but has additionally been shown to protect the cardiovascular system and act as a potent weight loss agent.
