“Conformity is the jailer of freedom and the enemy of growth.” – John F. Kennedy, 35th US president

Part 1: GLP−1 Receptor Agonists for the Treatment of Obesity

Glucagon-like peptide-1 receptor (GLP-1R) agonists represent a groundbreaking class of medications that target incretin hormone pathways. These receptors exhibit widespread distribution throughout the body, including neural tissues, pancreatic islets, cardiac muscle, pulmonary tissue, integumentary system, and numerous other organs. Extensive preclinical studies and robust clinical trials have demonstrated the remarkable efficacy of GLP-1R agonists in both treating and preventing obesity. By mimicking the effects of endogenous GLP-1, these agents not only promote satiety and reduce food intake but also enhance glucose homeostasis. Given their multifaceted therapeutic benefits and favorable safety profile, GLP-1R agonists have emerged as particularly promising therapeutic options for individuals struggling with obesity, offering a potential paradigm shift in obesity management.¹ 

Mechanism of Action

GLP-1RA medications employ multiple mechanisms to facilitate weight loss. These drugs mimic the glucagon-like peptide-1 hormone, which plays a vital role in blood sugar regulation and digestion. Their primary effects include reducing appetite and increasing calorie expenditure by activating brown fat tissue through the nervous system. At the metabolic level, medications like liraglutide and semaglutide stimulate insulin production while decreasing liver sugar production. They also slow gastric emptying, making them valuable for both type 2 diabetes management and weight reduction. Additionally, these medications regulate food intake through complex interactions with the gut-brain axis, influencing hunger-control centers in the brain and modulating the gut microbiome.² 

Liraglutide and semaglutide, although used for similar conditions, have distinct dosage guidelines and administration methods.

Semaglutide Dosage

For Diabetes (Ozempic®):

• Starting Dose: 0.25 mg weekly for the first four weeks.
• Increase to: 0.5 mg weekly after the first month.
• Possible Increase: Up to 1.0 mg or 2.0 mg weekly, depending on blood sugar control needs.

For Weight Management (Wegovy®):

• Starting Dose: 0.25 mg weekly.
• Monthly Increase: 0.25 mg increments until reaching 2.4 mg weekly.
• Purpose: Gradual increase manages side effects and medication adjustment.

Liraglutide Dosage

For Type 2 Diabetes (Victoza®):

• Starting Dose: 0.6 mg daily for the first week to allow the body to adjust.
• Increase to: 1.2 mg daily after one week.
• Possible Increase: Up to 1.8 mg daily, based on patient response.

For Weight Management (Saxenda®):

• Starting Dose: 0.6 mg daily.
• Weekly Increase: 0.6 mg increments until reaching 3.0 mg daily.
• Purpose: Gradual increase reduces stomach problems and aids in body adjustment.

Both medications are administered via injection, not oral pills. The injection pen, which comes pre-filled, makes it easy to set and deliver the correct dose. The injection sites are typically the stomach area, thigh, or upper arm.

The Good News

GLP-1RAs initially designed for treating type 2 diabetes mellitus (T2DM) had demonstrated weight loss benefits in several clinical trials.³ Victoza (liraglutide) and Ozempic (semaglutide), have since been approved by the Food and Drug Administration as weight loss medications due to their effectiveness in promoting significant and sustained weight loss.⁴ 

More Good News: May Not Appear to Increase Risk of Suicide

Although about a year ago, a study,⁵ that used 18 years’ worth of data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) found an association of patients reported suicidal ideation and/or depression while using GLP-1RAs medications. Compared with metformin and insulin, researchers found disproportionate reporting by patients using semaglutide and liraglutide. Other GLP-1RAs medications didn’t show this effect. The researchers did point out that these statistics don’t show causation — there’s no clear reason why those two medications were linked to more reports.

Further research has been more reassuring:

• Another study⁶ also used FAERS but looked only at data from 2018 to 2022, when usage of these drugs was ramping up, and found no link between suicidal or self-injurious behaviors and GLP-1RAs.
• A recent cohort study,⁷ which looked at data from nearly 300,000 people, found that GLP-1RAs users aren’t at increased risk for death by suicide.

Obesity increases the risk of a major chronic disease, so when an obese patient loses weight they also reduce their risk of cardiovascular disease, cancer, neurological diseases, etc. Recent studies have highlighted long-term benefits associated with weight loss from taking GLP-1RAs,⁸ including a marked reduction in cardiovascular events, heart failure, and kidney disease.

Semaglutide (Wegovy) and Cardiovascular Outcomes by Adiposity Changes

The SELECT trial demonstrated that semaglutide reduces major adverse cardiovascular events (MACE) in overweight or obese patients with cardiovascular disease but without diabetes. This prespecified analysis examines how baseline adiposity and treatment-induced changes relate to MACE risk.

17,604 patients (aged 45+, BMI ≥27 kg/m²) across 804 sites in 41 countries were randomized 1:1 to weekly semaglutide 2.4 mg or placebo. The primary outcome was time to first MACE (cardiovascular death, non-fatal heart attack, or non-fatal stroke). We analyzed adiposity measures (weight and waist circumference) at baseline, 20 weeks, and 104 weeks.

Semaglutide significantly reduced MACE across all baseline weight and waist circumference categories.

In the semaglutide group:

• Lower baseline weight and waist circumference predicted lower MACE risk (4% reduction per 5 kg lower weight; 4% reduction per 5 cm smaller waist).
• Greater waist circumference reduction correlated with lower MACE risk.
• Waist circumference reduction mediated an estimated 33% of semaglutide’s cardiovascular benefit.

In the placebo group:

• Lower baseline waist circumference (but not weight) predicted lower MACE risk.
• Weight loss paradoxically increased MACE risk.⁹ 

Semaglutide Usage is Associated With Reduced Hospitalizations in Patients With Obesity and Established Cardiovascular Disease 

This study examined whether semaglutide (a weight-loss medication) could reduce hospitalizations in patients with obesity and cardiovascular disease. Drawing from the SELECT clinical trial, researchers analyzed data from over 17,600 patients who were followed for about 3.5 years.

The key finding: patients treated with weekly semaglutide injections (2.4 mg) experienced approximately 10% fewer hospital admissions and spent about 11% fewer days in the hospital compared to those receiving placebo. This reduction applied both to all-cause hospitalizations and those related to serious adverse events.

These results are significant because they suggest semaglutide’s benefits extend beyond its known cardiovascular protective effects—it may also reduce the overall healthcare burden by keeping patients out of the hospital. The reductions were consistent across different patient subgroups, including variations in BMI, age, and sex.¹⁰ 

The Bad: Up to 40% Muscle Loss

Recent studies have shown that pharmacologic weight loss with GLP-1RAs and combination therapies is approaching magnitudes achieved with surgery. However, as more weight loss is achieved, there is concern for potential adverse effects on muscle quantity, composition, and function. Factors such as older age and prefrailty may influence the selection of appropriate candidates for these therapies because of risk for sarcopenia.¹¹ 

First off, despite substantial weight loss, many patients find staying on the medications difficult because of a lengthy list of uncomfortable side effects including nausea, vomiting, constipation, gastroparesis, dehydration, and gallstones.¹² 

Secondly, a new study published in the July 2024 journal Gastroenterology,¹³ found that GLP-1s can increase the risk of pulmonary aspiration when a patient is under deep sedation during surgery. This can cause aspiration pneumonia, a lung infection that occurs when food or liquid is inhaled into the lungs. It appears that routine fasting before a surgery doesn’t seem to be enough, so it’s suggested that patients stop these medications at least one week prior to surgery.

A commentary published in the November issue of The Lancet¹⁴ by an international team of researchers from the University of Alberta, McMaster and Louisiana State University who examined emerging research showing that up to 40% of the weight lost by people using weight-loss drugs is actually muscle.

Selected consequences of low muscle mass (or related conditions, such as sarcopenia, frailty, and cachexia) and malnutrition across aging and clinical populations. There is an extensive body of research reporting on the associations between low muscle mass and physical impairment or disability, falls and fractures, increased length of hospital stay, wound healing, need for rehabilitation, higher risk of post-operative complications, poor quality of life, tumor progression, increased treatment toxicity, and reduced survival.¹⁵ 

Ozempic May Weaken Muscles Despite Stable Size, Study Finds

As Ozempic use surges, so do concerns about muscle loss. New mouse research reveals a surprising twist: while muscle size changes less than expected, strength may still decline.

The Study’s Key Findings

Ozempic-induced weight loss reduced lean mass by 10% in mice. However, most lost weight came from organs like the liver—which shrank nearly 50%—rather than skeletal muscle. Skeletal muscles shrank only 6% on average, with some staying unchanged. Researchers note this partly reflects a return to baseline, since fat gain typically increases muscle mass as the body works harder to move around.

Strength vs. Size

The most intriguing finding: some muscles lost strength even when size remained stable, while others maintained both. This strength-size disconnect could particularly concern adults over 60, who face higher baseline risks for muscle loss.

“Loss of physical function strongly predicts both quality of life and longevity,” Funai explains.

What This Means

Researchers caution against direct human comparisons, since mice and humans gain weight differently. The study emphasizes the urgent need for clinical trials examining muscle strength changes—not just in Ozempic users, but for all future weight-loss drugs.

“There’s significant need for validation in humans, especially concerning muscle strength,” says co-author Takuya Karasawa, PhD.¹⁶ 

The Hidden Epidemic: Sarcopenia in Weight Loss and Aging

Key Points

• Sarcopenia, characterized by progressive muscle loss, significantly increases mortality risk.
• GLP-1 weight loss medications may accelerate muscle loss.
• Simple screening and prevention strategies exist but remain underutilized.
• Structured strength training and protein intake can effectively counter muscle loss.

Understanding Sarcopenia

Sarcopenia—from the Greek “sarco” (flesh) and “penia” (poverty)—represents the progressive loss of muscle mass and strength that accompanies aging. While some degree of muscle loss is inevitable, its acceleration can severely impact function and mortality. A recent meta-analysis of 56 studies found individuals with sarcopenia face double the mortality risk compared to those without.

Emerging Concerns with Modern Weight Loss

The increasing use of GLP-1 medications may inadvertently contribute to sarcopenia’s prevalence. 

Clinical Implications

Sarcopenia screening remains underutilized despite its significant impact on health outcomes. Notable statistics:

• 71% of hip fractures involve sarcopenia.
• 16-18% lifetime hip fracture risk in White women.
• 34% one-year mortality post-hip fracture.¹⁷ 
• GLP-1 have recently been found to shrink heart muscle in mice and human cells.

University of Alberta study¹⁸ in JACC: Basic to Translational Science. The authors say the research should serve as a “cautionary tale” about possible long-term health effects of these drugs.

“If people have been prescribed these drugs, then the benefits should likely far exceed the risks,” says Jason Dyck, senior author on the study, pediatrics professor in the Faculty of Medicine and Dentistry and a member of the Women and Children’s Health Research Institute. “However, the growing number of people who may be taking these drugs who do not meet the eligibility criteria and who are not at risk have a different risk-reward calculation that they should be made aware of.”

Dyck and his team set out to study why Ozempic (Semaglutide) causes loss of skeletal muscle. Using mice for the study, the researchers found that heart muscle also decreased in both obese and lean mice. The systemic effect observed in mice was then confirmed in cultured human heart cells.

Dyck, the Canada Research Chair in Molecular Medicine and head of the Cardiovascular Research Center, reports that mice with smaller hearts showed no harmful functional effects, suggesting minimal health impacts in humans. However, he notes that long-term effects or cardiac stress responses remain unknown.

“Given the growing number of people taking this drug who have no cardiovascular disease or who are not classified as obese, we suggest that cardiac structure and function be carefully evaluated in previous and ongoing clinical studies.”

GLP-1s and the Risk for Malnutrition

These questions reflect growing concerns among clinicians who see patients on GLP-1s unintentionally eat too little and become malnourished. A new study in Obesity Reviews confirms these worries, finding that many patients receive inadequate nutritional guidance, leaving them vulnerable to deficiencies.

“We see cases where people become so severely malnourished on GLP-1s that they need hospitalization,” said Rebecca Boswell, PhD, director of Penn Medicine Princeton Center for Eating Disorders. “It’s not uncommon.”

Malnutrition can disrupt body temperature, blood sugar, blood pressure, and electrolytes while causing vitamin deficiencies. Some symptoms—fatigue and lightheadedness—overlap with GLP-1 side effects, making careful assessment crucial. Consequences range from muscle loss and weakened immunity to poor wound healing, and in rare cases can be life-threatening.

“These meds are incredible for treating diabetes,” Boswell said. “My fear comes when they’re indicated for weight loss.” GLP-1 doses for weight loss exceed those for diabetes, yet research on higher-dose effects remains limited, especially in subpopulations like people with eating disorders.

The Thinking Around ‘Food Noise’

Lynn-Pullman, on Wegovy since May 2023, said the drug helped her win a lifelong battle with weight. After dropping 60 lb and reaching her goal weight in 2024, she’s remained on the medication, though she plans to discuss tapering her weekly dose with her physician.

The medication also helped her recognize “food noise,” a common phenomenon among overeaters.

“I didn’t understand what people meant by food noise until I experienced the change myself,” she said. “Before GLP-1, I couldn’t pass up a cookie or chocolate. Afternoons were always tough—I’d need to find something to snack on.”

Instead of “food noise,” psychologists call constant food thoughts “rumination,” said Kerri Boutelle, PhD, director of the Center for Healthy Eating and Activity Research at UC San Diego.

“Patients with bulimia or binge eating disorders will say, ‘It is calling me,'” Boutelle said. “They can’t get through their day without eating the cake in the refrigerator. They’re ruminating, thinking about food, planning food.”

Clinically, she said, “I’ve seen these drugs change people’s lives.”

But what if a GLP-1’s ability to silence food noise works too well, as it did for Lynn-Pullman, who didn’t realize she wasn’t getting enough calories? Or worse, what if a patient intentionally misuses a GLP-1 to quiet that food chatter?

A 2024 case report in the Journal of Clinical Psychopharmacology describes a woman with a history of anorexia who intentionally took more GLP-1 medication than prescribed to lose weight. She ended up in the emergency room multiple times with malnutrition-related symptoms and persistently refused to eat or take supplemental nutrition even when hospitalized.

Weight-loss drug companies’ marketing using the term “food noise” also concerns Boswell, especially for its influence on people with eating disorders. Abuse of diet pills and other diet aids is well-documented in medical literature, with some studies reporting prevalence rates around 50%.

“As eating disorder professionals, we think of food noise as hunger,” Boswell said. “GLP-1s turn down the volume on hunger—a dangerous signal to ignore. We developed hunger and food-related reward processing to prevent starvation. To turn away from hunger is to turn away from a powerful signal of what your body needs nutritionally to function at its best.”

She added, “GLP-1s make it very difficult, if not impossible, to engage in intuitive eating.”

Too Little Screening, Too Easy to Get

While science works to unravel the risks for malnutrition and other health issues linked to GLP-1s, millions of Americans are being prescribed the drugs, often outside close medical supervision. A May 2024 KFF national survey and August 2025 RAND survey found that 1 in 8 US adults had taken a GLP-1 drug. And reported similar results: 11.8% of Americans have tried a GLP-1 for weight loss, including about one-fifth of women aged 50-64.

“One of the biggest problems I’ve seen is how easily patients can order these online—through a brief telehealth evaluation—despite being at normal or below-normal weight, with no medical indication and an active eating disorder,” said Angela Guarda, MD, director of the Eating Disorders Program at Johns Hopkins Hospital.

Experts believe more stringent screening is needed before physicians prescribe GLP-1s for weight loss. This could ensure early identification of patients at risk for malnutrition, misuse, or abuse, as well as people with eating disorders.

“The screening process could mirror that used for bariatric surgery patients, which includes assessment for eating disorders and other mental health conditions,” Boswell said.

“Not just an initial assessment, but ongoing assessment. That isn’t happening currently. It’s really missing from clinical care around GLP-1s,” she said.

Nutrition counseling, mental health support, and closer medical monitoring should be part of the treatment plan for anyone on a GLP-1 for weight loss, said Ellen A. Schur, MD, MS, associate professor of medicine at the University of Washington School of Medicine. However, the cost of these support services may be prohibitive for many people.

What Lies Ahead?

Understanding the full impact of GLP-1s on the body will take time.

“I’ve been in weight management and eating disorders for 30-plus years, and weight management is not just about eating less and exercising more,” Boutelle said. “It’s incredibly complicated and multifactorial—genetics, metabolism, whether you were breastfed, your environment, sleep.”

Boswell said researchers need longitudinal data “from the start—looking at GLP-1 use from initial screening through continuation or discontinuation—to see how eating disorder symptoms and nutritional status change.”

She wants to better understand who is at risk of developing an eating disorder and malnutrition while on a GLP-1.

“Some people without eating problems can develop significant issues through overuse of these medications,” she said. “People who’ve lost weight on the medication and received positive reinforcement can develop hypervigilance around eating, social acceptance, and appearance.”¹⁹ 

Thyroid Cancer Risk

According to Dr. Varney, an assistant professor at the University of Virginia, thyroid cancer risks from GLP-1 weight loss medications mainly affect people with specific genetic conditions: multiple endocrine neoplasia 2 (MEN2) syndrome or medullary thyroid cancer (MTC). MTC is rare, accounting for only 3-5% of thyroid cancers.

The cancer risk depends on dosage. Animal studies used doses 8-60 times higher than human prescriptions, though some cases of thyroid cancer have been reported in humans taking these medications.²⁰ 

Pancreatitis and Gallbladder Concerns

When prescribing these medications, doctors must consider a patient’s history of pancreas inflammation (pancreatitis). While a family history of pancreatic cysts or cancer doesn’t prevent using these medications, they can increase gallbladder problems. Research from 2022²¹ shows higher risks of gallbladder disease, especially with higher doses and longer use.

These medications may not be suitable for patients with:

• Slow stomach emptying (gastroparesis)
• Eye problems from diabetes
• Severe constipation
• Serious heartburn.²² 

GLP-1 Drug Linked to Rare Vision-Threatening Side Effect

European regulators warn that semaglutide may cause sudden vision loss in approximately 1 in 10,000 users.

The popular weight-loss and diabetes drug semaglutide—sold under brand names Ozempic, Wegovy, and Rybelsus—can cause a rare but potentially blinding eye condition, European health authorities announced this week.

What Regulators Found

The European Medicines Agency (EMA) concluded that semaglutide increases the risk of non-arteritic anterior ischemic optic neuropathy (NAION), a condition that can cause sudden, permanent vision loss.²³ 

After reviewing all available safety data, the EMA’s Pharmacovigilance Risk Assessment Committee classified NAION as a “very rare” side effect, meaning it could affect up to one in 10,000 people taking the GLP-1 receptor agonist.

Warning Signs and Recommendations

Patients should seek immediate medical attention if they experience:

• Sudden vision loss
• Rapidly worsening eyesight

The EMA emphasized that if NAION is confirmed, semaglutide treatment should be discontinued immediately.

Supporting Research

This regulatory action follows mounting scientific evidence linking GLP-1 drugs to eye problems:

Recent Study Findings:

• Diabetes patients on semaglutide showed a 4-fold higher risk of developing NAION over 3 years compared to those not using GLP-1 medications.
• Patients using semaglutide for weight management faced an even higher 7-fold increased risk.²⁴ 

Broader Evidence:

• Multiple large epidemiological studies cited by the EMA found roughly a 2-fold increase in NAION risk among type 2 diabetes patients taking semaglutide.
• FDA adverse event data shows disproportionately higher NAION rates among semaglutide users compared to other GLP-1 drug users.

Regulatory Status

While the EMA has issued this formal warning, the FDA has not yet released similar guidance for GLP-1 drugs in the United States. However, US regulators are actively monitoring adverse event reports related to these medications.

GLP-1s Pose Heart Risks in Patients With HFrEF and Implants

Summary: A retrospective Canadian study of 106 patients with heart failure with reduced ejection fraction (HFrEF) and implanted cardiac devices found that GLP-1 receptor agonist use was associated with elevated heart rates (7 bpm higher), increased ventricular arrhythmias, and higher NT-proBNP levels compared to non-users. These findings suggest potential cardiac risks requiring monitoring in this patient population.

Topline:

Patients with HFrEF and implanted cardiac devices using GLP-1 receptor agonists had higher heart rates, more nonsustained ventricular tachycardia events, and elevated NT-proBNP levels compared to non-users.

Methodology:

• Retrospective analysis from a Canadian health center evaluated 106 patients with HFrEF and implanted cardiac devices (mean age 66 years; 81% men; mean BMI 31.4).
• Compared 53 patients who initiated GLP-1 therapy after device implantation with 53 non-users (January 2023–June 2024).
• Primary outcome: heart rate difference between groups. Secondary outcomes: arrhythmic events, BMI changes, and laboratory biomarkers.
• Follow-up duration: up to 1 year with device monitoring at four timepoints.

Takeaway:

• Heart rate was 7 bpm higher in GLP-1 users vs non-users (P < .01), reaching up to 13 bpm difference in the final evaluation phase.
• GLP-1 users had more nonsustained ventricular tachycardia events (3372 vs 399; P < .01) and total shocks or antitachycardia pacing therapies (33 vs 3; P = .01).
• NT-proBNP levels were significantly elevated in GLP-1 users, suggesting increased cardiac stress.
• BMI reduction was observed in GLP-1 users, though cardiovascular risks appeared to outweigh metabolic benefits in this population.²⁵

GLP-1 Receptor Agonist Use Linked to Chronic Cough Among Adults With Type 2 Diabetes

Those prescribed a GLP-1 RA had a significantly increased risk for new chronic cough compared with those prescribed any non-GLP-1 RA second-line medication, DPP-4 inhibitor, or sulfonylurea in a propensity score-matched analysis.

Tyler J. Gallagher, MD, MPH, from the Keck School of Medicine at the University of Southern California in Los Angeles, and colleagues examined the clinical association between GLP-1 RAs and chronic cough in a large multicenter cohort study using electronic medical record data from 70 health care organizations. Adults with type 2 diabetes and prescription of a GLP-1 RA were identified and compared to those prescribed another second-line diabetes medication (cohorts included 427,555 and 1,614,495 participants, respectively).

The researchers found that individuals prescribed a GLP-1 RA had a significantly increased risk for new chronic cough compared with those prescribed any non-GLP-1 RA second-line medication, dipeptidyl peptidase-4 (DPP-4) inhibitor, or sulfonylurea in a propensity score-matched analysis (adjusted hazard ratios, 1.12, 1.18, and 1.32, respectively). This finding was not seen compared with those prescribed a sodium-glucose cotransporter 2 (SGLT2) inhibitor. After removing patients with a previous diagnosis of gastroesophageal reflux, those prescribed GLP-1 RAs had a significantly increased risk for chronic cough compared with those prescribed any non-GLP-1 RA, DPP-4 inhibitor, SGLT2 inhibitor, or sulfonylurea (adjusted hazard ratios, 1.29, 1.36, 1.14, and 1.25, respectively).

“This cohort study suggests that there is an association between GLP-1 receptor agonist use and new diagnosis of chronic cough,” the authors write. “This association was present even among patients without a diagnosis of gastroesophageal reflux disease.”²⁶ 

‘Ozempic Teeth’: Another Effect of GLP-1 Agonists?

Reports of “Ozempic mouth” and “Ozempic teeth” describe oral health problems—gum inflammation, tooth decay, and bad breath—primarily linked to dry mouth.

“All GLP-1 agonists cause changes in GI tract secretions,” says Ann Marie Defnet, MD, an obesity medicine specialist at Northwell Health. “This definitely impacts saliva.”

GLP-1 users also tend toward dehydration since the drugs suppress hunger and thirst, Defnet notes. While she hasn’t seen severe periodontal disease in her practice, patients frequently report feeling dehydrated.

“The serious oral health issues reported likely represent later-stage problems in patients who aren’t staying hydrated,” Defnet explains. She counsels patients to drink water regularly, even without feeling thirsty, which helps alleviate symptoms.

However, many GLP-1 users lack medical supervision and proper counseling, allowing dehydration to compound and further reduce saliva production.

Reduced saliva and dehydration can cause bad breath, though patients in ketosis may also experience a characteristic fruity odor—particularly those avoiding fats entirely.

About 25% of GLP-1 users experience GI issues, primarily bloating, nausea, diarrhea, and constipation. Vomiting, while uncommon, requires medical attention. “If you’re vomiting enough to develop periodontal disease, you shouldn’t be on a GLP-1,” Defnet warns. Post-vomiting dental care is crucial to remove acid from teeth and mouth.

“These mouth symptoms indicate you need better self-care while taking these drugs,” Defnet emphasizes. “They’re not benign—they have side effects. But proper hydration and a balanced diet can alleviate many problems.”

Defnet stresses the importance of medication transparency with all healthcare providers. Dentists should know about GLP-1 use since it affects saliva and periodontal health, even if they don’t prescribe these medications.

“Many medications affect oral health,” she concludes. “Honesty about all medications is essential.”²⁷ 

GLP-1s May Double Colorectal Cancer Risk

A new meta-analysis of over 5 million patients suggests GLP-1 receptor agonists could significantly increase colorectal cancer risk.

Key Findings

Researchers analyzed seven retrospective studies involving 5,066,681 patients with type 2 diabetes. The pooled analysis found GLP-1 users had more than double the risk of colorectal cancer (relative risk: 2.31).

However, when comparing GLP-1s directly to other diabetes drugs like metformin, the increased cancer risk wasn’t statistically significant—suggesting the elevated risk may be related to diabetes itself rather than the medication.

Potential Causes

Researchers propose several mechanisms:

• Intestinal tissue changes
• Altered gut bacteria
• Increased cell turnover in digestive tract

Notably, major cardiovascular trials like LEADER haven’t consistently shown increased cancer rates, leaving questions about whether GLP-1s directly cause cancer.

Clinical Implications

Study author Dr. Ying Zhong from West China Hospital emphasized the need for larger, long-term clinical trials. The researchers recommend:

• Careful risk-benefit analysis before prescribing
• Further investigation into long-term safety²⁸ 

GLP-1 Receptor Agonists and Cancer Risk in Adults With Obesity

A retrospective cohort study of 86,632 adults with obesity published in JAMA Oncology investigated the association between GLP-1 receptor agonists (GLP-1RAs) and cancer risk. The study found a 13% reduction in overall cancer incidence among GLP-1RA users, with significant risk reductions for endometrial, ovarian, and meningioma cancers. While the findings suggest potential protective effects, particularly among younger women with metabolic risk factors, the authors emphasized that the observational study design precludes establishing direct causality.²⁹ 

GLP-1 Receptor Agonists and Hair Loss

A large retrospective cohort study presented at the 2025 European Academy of Dermatology and Venereology Congress found that GLP-1 receptor agonists significantly increase the risk of hair loss. Researchers analyzed data from nearly 548,000 GLP-1 users and an equal number of non-users over a 10-year period (2014-2024).

Key findings showed that at 12 months, GLP-1 users had a 76% higher risk of telogen effluvium, 64% higher risk of androgenic alopecia, and 40% higher risk of nonscarring hair loss overall compared to non-users. Notably, no association was found with alopecia areata.

Experts suggest this hair loss may represent an “unmasking” of underlying androgenic alopecia triggered by rapid weight loss rather than direct drug toxicity. The condition is typically reversible, and recommendations include counseling patients upfront, pacing weight loss, maintaining proper nutrition, and screening for contributing factors like iron deficiency.³⁰ 

Discontinuing GLP-1 Receptor Agonist Use Before Pregnancy Tied to Risk for Adverse Outcomes

Compared with unexposed pregnancies, the GLP-1 RA group had a higher risk for excess gestational weight gain, and a higher risk for preterm delivery, gestational diabetes, and hypertensive disorders of pregnancy.

Summary

• A retrospective cohort study of 149,790 singleton pregnancies examined the impact of GLP-1 receptor agonist (GLP-1 RA) exposure and discontinuation before or during early pregnancy.
• GLP-1 RA-exposed pregnancies showed significantly greater gestational weight gain (mean 13.7 kg vs. 10.5 kg), with a 1.32 risk ratio for excess weight gain.
• Increased risks were observed for adverse pregnancy outcomes, including:
  • 1.34 risk ratio for preterm delivery
  • 1.30 risk ratio for gestational diabetes
  • 1.29 risk ratio for hypertensive disorders of pregnancy
• The study highlights the potential risks associated with GLP-1 RA discontinuation and calls for further research to understand the long-term implications and develop risk mitigation strategies.

HealthDay News — Glucagon-like peptide-1 receptor agonist (GLP-1 RA) use with subsequent prepregnancy or early pregnancy discontinuation is associated with more gestational weight gain and a higher risk for preterm delivery, gestational diabetes, and hypertensive disorders of pregnancy, according to a study published online November 24 in the Journal of the American Medical Association.

Jacqueline Maya, MD, from Massachusetts General Hospital-Mass General Brigham in Boston, and colleagues conducted a retrospective cohort study of 149,790 singleton pregnancies delivered between June 1, 2016, and March 31, 2025, to compare weight gain and pregnancy outcomes with and without exposure to GLP-1 RAs before or during early pregnancy. The primary analysis included 1792 matched pregnancies (448 exposed [84% with obesity and 23% with preexisting diabetes] and 1344 unexposed).

The researchers found that the GLP-1 RA-exposed pregnancies had greater gestational weight gain than propensity score-matched unexposed pregnancies (mean, 13.7 vs 10.5kg). Compared with unexposed pregnancies, the GLP-1 RA-exposed group had a higher risk for excess gestational weight gain (risk ratio, 1.32), greater mean birth weight percentile (58.4 vs 54.8%), and a higher risk for preterm delivery, gestational diabetes, and hypertensive disorders of pregnancy (risk ratios, 1.34, 1.30, and 1.29, respectively). No difference was seen in birth length, risk for large- or small-for-gestational-age birth weight, or cesarean delivery.

“Additional studies are needed on the balance of prepregnancy benefits of GLP-1s with the risks associated with interrupting them for pregnancy,” senior author Camille E. Powe, MD, also from Mass General Brigham, said in a statement. “We need to do more research to find ways to help manage weight gain and reduce risks during pregnancy when stopping GLP-1 medications.”³¹ 

The Ugly – When You Stop You Not Only Gain the Weight Back but You Gain More Body Fat

While clinical trials show that GLP-1RA medications effectively help with weight loss and improve other health measures, they can cause digestive side effects. An important consideration is what happens when people stop taking these medications: even if they maintain a healthy diet and exercise habits, most people regain the weight they lost.

Researchers have known for a long time that there has been a noticeable trend of quick weight regain following the discontinuation of semaglutide and other GLP-1 RAs, as detailed in various trials.³² 

During weight loss, several biological changes compensate for and prevent the maintenance of long-term weight loss, and weight regain is commonly observed.³³ 

Research has found several reasons for this weight regain after stopping the medication. These include changes in brain signaling, reduced hormone production, and the body’s natural tendency to adapt to weight loss by trying to return to its previous weight.³⁴ 

One of the things I think is really important is that, from the get-go on starting on these hormones, people start working with Mederi Care approach to health optimization and healthy weight management.

“Out of your vulnerabilities will come your strength.”

– Sigmund Freud, neurologist and founder of psychoanalysis

What Patients Should Know Before Using GLP-1 RAs

Not every overweight patient is a good candidate for GLP-1 RAs, and it’s important that doctors explain why the medications may not be right for them, Davisson said.

“If a patient only has a few pounds to lose (15-20 lb) and does not accept that these medications are intended to be a long-term treatment for the chronic diseases of diabetes or obesity, then they might not be a good candidate for the medication,” Davisson said.

Also essential is making sure patients are willing to follow appropriate healthy eating guidelines when on the medications, including getting enough protein and produce to maintain lean body mass and the necessary fiber to keep bowel habits regular.

Varney often hears concerns from physicians about the long-term effects of GLP-1 RAs. She said this class of medications has been used for nearly 20 years to treat type 2 diabetes, and the data over the past two decades have shown that the benefits of GLP-1 RAs far outweigh the risks for most patients.

I have written a wonderful chapter in my book, Adaptogens in Medical Herbalism on weight management. Two previous blogs of mine that will also help with a truly holistic approach to weight management and being the best version of yourself.

1. Six Targets For Optimal Weight Using Botanicals – https://www.donnieyance.com/six-targets-for-optimal-weight-using-botanicals/
2. How To Be Healthy and Happy Achieving Your Optimal Weight https://www.donnieyance.com/how-to-be-healthy-and-happy-achieving-your-optimal-weight/

The Energy Balance Dance 

The importance of skeletal muscle mass is increasingly being recognized in the medical field. The crucial roles of skeletal muscle have come to the forefront of public attention due to data on the use of GLP-1 receptor agonists, which are effective for weight loss, but can cause substantial muscle loss. Beyond its obvious role in movement and physical function, skeletal muscle serves as the body’s largest reservoir of amino acids, plays a vital role in metabolic health, and functions as an endocrine organ secreting various myokines that influence whole-body metabolism. Recent clinical evidence has demonstrated that maintaining adequate muscle mass is essential for healthy aging, improved chronic disease outcomes, and enhanced recovery from acute illness. The emergence of popular weight loss medications like semaglutide and tirzepatide has highlighted the critical need to understand and preserve muscle mass during weight loss interventions, as the loss of muscle tissue could potentially compromise these important physiological functions.³⁵ 

The first thing to keep in mind is that your body weight isn’t just about calories in and calories out. Sure, that’s part of the equation, but there’s a deeper story happening beneath the surface. 

Here’s a thought that might change how you look at your next meal: Every time you choose what to eat, you’re actually making two choices at once. It’s a fascinating way to think about food that goes beyond the usual “good versus bad” conversation.

Think of it this way – when you reach for a processed snack instead of something whole and natural, you’re not just consuming something that might harm your health. You’re also missing a golden opportunity to give your body something healing and nourishing. It’s like turning down natural medicine while taking something that makes you feel worse.

But here’s where we can flip the script. Instead of carrying around a mental list of foods to avoid (which, let’s face it, can be exhausting), what if we got excited about all the incredible foods we can eat? This isn’t just positive thinking – it’s a powerful way to transform your health.

Your grocery store’s produce section is really nature’s pharmacy in disguise. Those vibrant fruits and vegetables aren’t just pretty to look at – they’re packages of natural medicine. Each color, from deep purple berries to bright green leafy vegetables, represents different compounds that can heal and protect your body.

When you start thinking this way, healthy eating becomes less about restriction and more about opportunity. Instead of asking “What should I avoid?” try asking “What healing foods can I add to this meal?” This simple shift can transform eating from a source of stress into an act of self-care. The beauty of this approach is that when you focus on adding good things to your diet, the less healthy choices naturally get crowded out. Think of your body as an intricate symphony where every instrument needs to play in perfect harmony. 

The Fast Food Factor 

Our modern world has brought us convenience, but at what cost? Fast food, with its perfect storm of high calories, processed ingredients, and easy accessibility, has changed the way we eat. These foods don’t just add calories to our diet – they actually change how our bodies process energy. It’s like switching from a precision-engineered engine to one that’s running on the wrong fuel.

The Hidden Players: Blood Sugar and Fat Metabolism Here’s where things get really interesting. Two key players in this complex dance are:

• Blood Sugar (Hyperglycemia): When we consistently flood our bodies with high-calorie, processed foods, our blood sugar regulation system starts to falter. It’s like constantly revving a car engine – eventually, something’s got to give.
• Fat Processing (Dyslipidemia): Our bodies have an amazing ability to process and store fats, but modern diets can overwhelm this system. Think of it as trying to force too much traffic through a small street – eventually, everything backs up.

The Complex Web 

What makes obesity such a challenging issue is how these factors interact with each other. Your blood sugar levels affect your fat storage, which influences your energy levels, which impacts your activity, which circles back to affect your blood sugar… it’s a continuous cycle where each element influences the others.

Why This Matters 

Understanding this complexity is crucial because it helps us realize why simple “eat less, move more” advice often falls short. It’s not just about willpower or counting calories – it’s about understanding and working with your body’s intricate systems.

A Better Approach 

Instead of focusing solely on calories, consider:

• The quality of your food choices
• How different foods affect your blood sugar
• The timing of your meals
• Your body’s unique way of processing nutrients.³⁶ 

Obesity is associated with a wide range of metabolic dysfunctions, which affect multiple organs of the body and subsequently disrupt their regular function.

Interconnection between genetic factors, environmental factors, dietary pattern and gut microbiota associated with the incidence of obesity.³⁷ 

Think of it as tuning that symphony we talked about earlier – every instrument needs attention, not just the loudest ones. Instead of falling for quick fixes or extreme diets, we can work with our bodies’ natural systems to find balance and health. Remember, your body is incredibly complex and wonderful. By understanding and respecting this complexity, we can make more informed choices about our health and well-being. One of the basic concepts and directives of the Unitive System, called Mederi Care, is to enhance anabolic metabolism, efficiency and auto-regulation; at the molecular, cellular and organ system levels.

The Intricate Relationship Between Gut Health and GLP-1

One of the most exciting insights into GLP-1 is the role of the gut microbiome in its production. Research has identified specific beneficial bacteria that play crucial roles in GLP-1 secretion and overall metabolic health. These microorganisms work through complex mechanisms, primarily through the production of short-chain fatty acids (SCFAs), to influence our body’s GLP-1 levels.

Key Bacterial Players in GLP-1 Production

Several beneficial bacteria have emerged as important contributors to GLP-1 regulation:

1. Akkermansia muciniphila: This beneficial bacteria stimulates GLP-1 secretion while maintaining gut lining integrity. Research shows that individuals with higher Akkermansia levels typically demonstrate better metabolic health markers and lower obesity risk.
2. Clostridium butyricum: Known for its production of butyrate, a vital SCFA that promotes GLP-1 secretion. Butyrate’s benefits extend beyond GLP-1, including reduced inflammation and enhanced gut barrier function.
3. Bifidobacterium infantis: While indirectly affecting GLP-1, this bacteria produces essential metabolites that support other beneficial bacteria, helping maintain a balanced gut ecosystem.

Dietary Interventions to Optimize GLP-1 Levels

A diet rich in specific nutrients can naturally enhance GLP-1 production through the gut microbiome:

• Fiber-Rich Foods: Include plenty of vegetables, fruits, potatoes, and whole grains.
• Polyphenol Sources: Incorporate berries, leafy greens, and nuts.
• Probiotic-Rich Foods: Add fermented foods to support beneficial bacteria.

Anabolic – Catabolic and Metabolic Optimization

An adequate balance between catabolic (mobilization of energy) and anabolic processes (growth, healing) is considered necessary for long-term health and survival. In modern society, which is characterized by a rapid pace of life, high demands, efficiency and competitiveness, it is likely that lack of rest, recovery and restitution is a greater health problem than the absolute level of stress.

Adequate intake of high-quality absorbable protein is essential for optimum immune response and for enhancing lean muscle mass. Since antibodies are protein structures, low protein intake or poor protein utilization can lead to low antibody production and/or decreased surveillance and a poor immune response. Proteins, a vital component of all human cells, are continually being built up and broken down to their building block peptides, the amino acids. 

A decline in protein synthesis (increases catabolic activity) is the single most important indication of aging. As muscle mass diminishes, muscle strength begins its downfall. This catabolic process also results in decreased muscle strength, heart health, bone density, obesity, impaired glucose metabolism and an increase in aging, and reduction in quality of life. Anabolic restoration with diet, exercise, rest, and botanical and nutritional formulations, is the core to my approach to both health promoting, disease prevention, and for healthy aging. The importance of enhancing cellular protein synthesis cannot be overstated. Aging causes a decline in protein synthesis that inevitably leads to disability and death. It is the single most overlooked and under-treated key factor to health there is. Scientists have found that administering amino acid mixtures of creatine, HMB, glutamine with co-factors such as boron, chromium and vanadium, increased net muscle protein synthesis by increasing amino acid transport into muscle cells. Other anabolic-immunonutrients include the amino acids L-arginine or L-citrulline, and carnitine. This increased amino acid delivery to the cells stimulates muscle protein synthesis and prevents weakness throughout the body including the heart, lungs, brain, liver, immune system, and bones. An anabolic response achieved with amino acid and anabolic botanical compounds indicate that muscle mass could be preserved and/or restored.

Who Is at Risk for Too Little Protein?

A study from 2018 found that 23% of US adolescent girls (aged 14 to 18 years old) and 11% of adolescent boys were consuming below the RDA for protein, which may compromise their growth and development.⁴⁰  This is thought to be related to the growing independence in food choices and the high prevalence of dieting in this group.

Low protein intake is also a concern for the elderly in the US. The same 2018 study found that among those 71 years and older, 19% of women and 13% of men consume less protein than the RDA.⁴¹  This is a particular concern in this age group, as loss of muscle is accelerated with aging, and that can lead to greater frailty, loss of balance, and greater risk of falls. Some researchers argue that older adults actually need more protein than recommended by the RDA in order to maintain muscle mass and function.⁴² 

Consuming more than this amount of protein per day provides no additional benefit, and quality of the protein is as important as the quality. Both, too little and too much protein aren’t helpful and might actually be harmful. Current evidence indicates it’s large amounts of animal protein (particularly from red meat or processed meats) that can be problematic.⁴³ 

Results of pooled studies conducted on humans to date indicate that the integration of WPC in the diet of resistance-trained individuals is effective in order to maximize muscle mass accession. Nonetheless, the observed improvements are minimized when the total daily protein intake reaches a minimum of ≥1.6 g/kg. Under resting conditions, a single serving of ~0.24 g/kg body mass seems to be enough for stimulating a maximal postprandial response of muscle protein synthesis.⁴⁴  

In another study, from 2015, frequent consumption of red meat in adolescence was associated with a higher risk of breast cancer later in life, whereas consuming poultry, fish, legumes, and nuts instead lowered risk.⁴⁵ 

Just as important as the amount of the type – it’s not just the quantity of protein that matters, but also the nutritional package that it comes in.

The specifics of protein supplementation (eg, timing, postexercise protein dose or protein source) play a minor, if any, role in determining resistance exercise training-induced gains in fat-free mass and strength over a period of weeks.⁴⁶ 

So quality is more important than quantity, and though specific isolated amino acids do contribute to the totality of protein, they do act on muscle protein synthesis aiding in muscle recovery and mass.

Resistance exercise and protein supplementation can be particularly beneficial in older adults, who are at risk for progressive loss of skeletal muscle mass and strength (known medically as sarcopenia), which may increase fall risk.⁴⁷ 

How the Botanical and Nutritional Toolbox Can Be Used to Mitigate the Negative Effects of GLP-1 RAs, to Enhance Lean Muscle Mass, Reduce Level of Body Fat, and Keep it Off

Several types of diets are being studied to find a model that has the quality and quantity of nutrients to promote weight loss, reduction of body fat, maintenance of muscle mass and satiety control and most of the research points to using a high quality Undenatured Whey Protein Concentrate and a major nutritional supplemental aid.⁴⁸ 

Frestedt, et al. demonstrated that the supplementation with a mixture of whey protein isolate with other peptides (2 servings/day and each serving with 10 g protein) for 54 healthy subjects for 12 weeks, in addition to 47 control subjects who consumed glucose (10 g/serving) led to weight loss in both groups, but the group supplemented with whey protein had higher weight loss. They also had greater reductions of body fat (6.1%) and a higher maintenance of lean mass than the control group who had consumed just glucose.⁴⁹ 

Undenatured Whey Protein Concentrate (WPC)

Undenatured Whey Protein Concentrate (WPC) is one of the highest-quality proteins given its amino acid content (high essential, branched-chain, and leucine amino acid content) and rapid digestibility. Consumption of WPC has a robust ability to stimulate muscle protein synthesis.⁵⁰ WPC leaves up to 99% of the peptides undamaged. WPC has the highest protein efficiency ratio, the highest biological value, and scores the highest on the protein digestibility corrected amino acid score.  WPC is composed of alpha-lactoglobulin, beta-lactoglobulin, bovine serum albumin, and immunoglobulins (IgG1, IgG2, secretory IgA, and IgM). Other components of the lactalbumin fraction include: enzymes, iron binding proteins, calcium, potassium, sodium, phosphorous, and vitamins A, C, B₁, B₂, B₃, B₅, B₁₂, folic acid, and biotin.^51,52 

“WPC has an attractive effect on glucose metabolism control in healthy, overweight, obese, and insulin-resistant subjects. Moreover, whey protein assures a higher satiety; this effect is involved with the modulation of several gut hormones related to the reduction of food intake, with increased release of anorectic hormones, such as cholecystokinin, leptin, and GLP-1 and decreased release of the orexigenic hormone, ghrelin; and reduction of neuropeptide Y and increase of pro-opiomelanocortin in CNS. In addition, the reductions of expression of both inflammatory and oxidative stress markers, as well as the reduction in blood pressure, are also the main beneficial of risk factors for metabolic diseases.”⁵³ 

Effect of WPC Supplementation on Weight and Body Composition Indicators: A Meta-Analysis of Randomized Clinical Trials

Thirty-five Randomized Controlled Trials (RCTs), with a total of 1902 adult participants were included in pooled analysis. The data from trials currently available supports the use of WP to improve body composition indicators. The benefits of WPC on body composition are expected to be greatest when combined with resistance training and a reduction in overall calorie consumption.⁵⁴

WPC supplementation improves recovery of muscle function following resistance training (A systematic review and meta-analysis).^{55 s}

WPC supplementation improves sarcopenia in older adults: a systematic review and meta-analysis of randomized controlled trials of with or without resistance training.

This meta-analysis study was registered in PROSPERO (CRD42023407885). Ten RCT studies, including 1154 participants, were included and analyzed. The primary outcomes were the changes in muscle mass, strength, and physical performance.

This review confirms that WPC can improve various aspects of older adult with sarcopenia, thereby enhancing their overall physical condition.⁵⁶ 

In one study WPC supplementation improved body composition in 262 sarcopenic tube fed patients.⁵⁷ 

WPC is effective at limiting body fat expansion. An animal study found that body-fat gain was 21% lower in WPC supplemented group compared to a group taking casein over a 7-week period. Plasma insulin was lowered in this group, as well.⁵⁸ 

HMB: The Hidden Hero of Muscle Health 

What is HMB? Let’s start with its full name: ß-hydroxy-ß-methylbutyrate. Don’t worry about pronouncing it – we’ll stick with HMB! It’s a natural substance your body produces in muscle cells, and you can also find it in everyday foods like avocados, citrus fruits, cauliflower, and even catfish. Think of it as one of nature’s building blocks for maintaining strong, healthy muscles.

Why Your Body Loves HMB 

Here’s what makes HMB fascinating: it’s like a guardian for your muscles. Imagine your muscles as a house – HMB helps with both construction (building new muscle) and maintenance (preventing breakdown). It’s particularly good at helping your body maintain what scientists call “lean body mass” or LBM – essentially, all the good stuff in your body that isn’t fat.⁵⁹ 

This matters more than you might think. Your lean body mass isn’t just about looking fit; it’s crucial for:

• Supporting your immune system
• Maintaining healthy skin
• Helping wounds heal properly
• Keeping your organs functioning well
• Maintaining physical strength and independence

The Science Behind the Magic 

Recent research has shown something remarkable about HMB: it works through what scientists call “anticatabolic mechanisms.” In plain English? It helps prevent muscle breakdown while encouraging muscle growth. It’s like having a security system and a construction crew working together to protect and improve your muscles.⁶⁰ 

Who Needs to Know About HMB? 

While athletes have known about HMB for years, using it to enhance performance and build muscle, its benefits go far beyond the gym. Recent studies have shown promising results for:

• Older adults wanting to maintain strength and independence
• People dealing with chronic illness
• Those taking certain medications (like GLP-1 inhibitors) who want to maintain muscle mass
• Anyone interested in protecting their muscle health long-term

Natural Sources of HMB include avocados, citrus fruits, and cauliflower. However, for therapeutic benefits, some people might need additional supplementation – especially older adults or those dealing with specific health conditions.

Remember, maintaining muscle mass isn’t just about looking good – it’s about staying healthy, independent, and resilient throughout your life. HMB might just be the unsung hero helping you achieve these goals.⁶¹ 

The Creatine Connection 

Now, let’s clear up a common misconception about creatine. Many people think it’s just for bodybuilders, but that’s like saying water is just for fish. The right form of creatine, especially when paired with magnesium, is more like a cellular battery charger. It helps keep your energy levels up, supports your brain function, and aids in recovery – whether you’re an athlete or just someone wanting to stay healthy and active.

Creatine supplementation among pre-menopausal females appears to be effective for improving strength and exercise performance. Post-menopausal females may also experience benefits in skeletal muscle size and function and favorable effects on bone when combined with resistance training. Pre-clinical and clinical evidence indicates positive effects from creatine supplementation on mood and cognition, possibly by restoring brain energy levels and homeostasis. Creatine supplementation may be even more effective for females by supporting a pro-energetic environment in the brain.⁶³ 

Creatine supplementation mitigates skeletal muscle weakness in cancer patients on chemotherapy.⁶⁴ 

“Creatine MagnaPower” (MP) is a patented magnesium creatine chelate that provides the body with a readily available source of magnesium while also making the creatine more active by protecting it from cyclization. This patented mineral amino acid chelate contributes to an overall positive impact on many functions including, but not limited to, a non-steroidal anabolic enhancing effect. Creatine MP will also provide rehydration and endurance to a person showing signs of physiological stress.

Creatine MP is one of the most important nutrients to be combined with anabolic botanicals, such as Rhaponticum c. to provide the body with a one-two punch of plant compounds together with amino acid peptides for cellular restoration, and to build the build body up for muscle recovery as well as vital organ enhancement.

Glutamine

Glutamine is the most abundant amino acid in the blood and is a free amino acid in the human body. Glutamine levels decline markedly during periods of injury, illness, trauma, radiation therapy and stress, leading to muscle wasting. Glutamine supplementation prevents immunosuppression, muscle atrophy during periods of stress, heals gastric and peptic ulcers, and is a chemotherapy and radiation therapy protectant compound. Glutamine’s effects on the gastrointestinal tract appears to be due to its use as a vital nutrient by both the intestinal immune cells and mucosal cells. Without sufficient glutamine, muscles begin to atrophy. Although, glutamine is not considered an essential amino acid, its importance in our overall health during times of stress make it conditionally essential.^65,66 

Glutamine has emerged as a promising therapeutic agent due to its diverse physiological functions. It serves as a crucial precursor in the synthesis of several important antioxidant molecules, including reduced glutathione, which acts as a primary cellular defense against oxidative damage. Additionally, Glutamine supports the production of vital cofactors NAD(H) and NADP(H), which are essential for numerous redox reactions in the body. Furthermore, Glutamine plays a role in nitric oxide synthesis, a molecule critical for vascular function.⁶⁷  

Glutamine supplementation prevents muscle catabolism, promotes muscle anabolism, which is basically muscle growth, enhances the immune system, and enhances glycogen storage.^68,69 

Glutamine supplementation improves the benefits of combined-exercise training on oral redox balance and inflammatory status in elderly individuals.⁷⁰ Glutamine supplementation improves insulin sensitivity in critically ill patients, and prevents obesity.⁷¹ 

Citrulline

Citrulline is a non-essential amino acid that is synthesized almost exclusively by the intestines and has a regulatory key role in nitrogen homeostasis. Circulating citrulline comes mainly from glutamine metabolism and endogenous synthesis of intestinal arginase, and is abundantly found in watermelon (primarily the rind).⁷² 

Citrulline is a nitric-oxide (NO)-stimulating amino acid that increases muscle performance and augments training adaptations. Endogenous NO relies on the precursors L-citrulline (better than L-arginine) serving as an effective precursor of L-arginine. NO plays a critical role in endothelial function, promoting relaxation of vascular smooth muscle and subsequent dilation. This reaction leads to smooth muscle relaxation and vasodilation. Enhanced NO bioavailability and vasodilation may also aid aerobic and anaerobic metabolism, reduce the oxygen (O₂) and ATP cost of exercise, improve mitochondrial efficiency, and improve muscle contractility.⁷³ 

A systematic review and meta-analysis found that Citrulline supplementation combined with exercise improved body composition and lower limb function of overweight older adults.⁷⁴

In another study Citrulline supplementation and aerobic training stimulated endothelial NO mediated vasodilation, leading to improvements in organ perfusion, blood pressure, arterial stiffness, atherosclerosis and metabolic health (glucose control and lipid profile). This study suggest that Citrulline supplementation and exercise training can be an effective strategy to counteract the adverse effects of obesity on vascular function in older adults.⁷⁵ 

Oral l-citrulline provides greater plasma l-arginine levels due to an efficient conversion of citrulline to arginine.⁷⁶ Recent data have shown that oral citrulline treatment reduced peripheral BP by improving aortic relaxation in animals.^77-80 

Vitamin D: The Sunshine Nutrient Your Muscles Can’t Live Without

Think of vitamin D as your body’s master key – it unlocks so many doors to better health that scientists are still discovering new ones. While most of us know it’s important for strong bones, there’s a fascinating story about how this sunshine vitamin keeps your muscles strong and healthy that deserves attention.⁸¹ 

Your muscles actually have special receptors specifically designed to welcome this vitamin, like lock and key.⁸² When your body doesn’t get enough vitamin D, these receptors start to lose their function – imagine a key that’s slowly wearing down and no longer fits the lock properly. This breakdown can lead to muscle weakness and poor performance.

Inside your muscle cells, vitamin D works like an orchestra conductor, directing various essential processes. It helps your cellular powerhouses (called mitochondria) produce energy more efficiently and fights off damaging oxidative stress – think of it as both a power boost and a shield for your muscles.⁸³ Vitamin D is crucial for mitochondrial oxidative phosphorylation capacity; an important driver of muscle regeneration.⁸⁴ 

Vitamin D is also a crucial player in your immune system. It acts like a wise mediator, helping to calm down excessive inflammation while supporting your body’s natural defense mechanisms.^85,86 It’s like having a skilled diplomat working inside your body, making sure everything runs smoothly and peacefully.

Research has shown that people with low vitamin D levels are more likely to experience this age-related muscle loss. The good news? Studies suggest that vitamin D supplementation can help improve muscle strength and physical performance, particularly in older adults.⁸⁷ 

While sunlight is our natural source of vitamin D, many of us don’t get enough through sun exposure alone. Talk to your healthcare provider about checking your vitamin D levels and whether supplementation might be right for you. Be sure to check both vitamin D 25 OH and 125 diOH. I recommend a natural/whole-food form of vitamin D combined with vitamin K, and red palm oil extract, a rich source of water-soluble vitamin A from highly absorbable carotenoids.^88,89 

Botanicals with Enhanced Anabolic Effects

Some of my favorite botanicals for enhancing anabolic health and assisting the immunonutrients include Rhaponticum carthamoides, Epimedium spp., Eurycoma jack, Tribulus terrestris, Mucuna puriens, Shilajit, also known as Mumie, and Cissus quadrangularis. I will expand a bit on Rhaponticum, my #1 favorite medicinal herb.

Rhaponticum (Rhaponticum carthamoides)R. carthamoides grows in the pristine alpine and subalpine zones and alpine meadows of Southern Siberia. The root and underground stems of Rhaponticum are valued as powerful medicines in Siberian folk medicine where it has been used for centuries to treat fatigue, anemia and impotence. Noted for its ability to support recovery from disease,15 Rhaponticum was also used to strengthen those suffering from weakness after illness or from overwork.⁹⁰ 

Rhaponticum is an adaptogenic herb that specifically helps prevent the catabolic state seen with chronic stress. A rich source of potent anabolic compounds, called ecdysterones, Rhaponticum has been researched for over 40 years. It is acknowledged for its powerful adaptogenic ability and found to prevent the catabolic state seen with chronic stress.⁹¹ 

In clinical studies, a standardized extract of Rhaponticum revealed anabolic properties attributed to its ecdysterone constituents.⁹² It is noted for its ability to increase protein biosynthesis and to enhance physical and mental work capacity along with physical performance and endurance.⁹³ It modulates immune function, exerts antioxidant activity and enhances cardiovascular functions.⁹⁴ The mechanism by which ecdysteroids act is binding with signal transduction pathways, rather than with steroid receptors. More than 200 ecdysteroid compounds are described, 50 of which are isolated from Rhaponthicum carthamoides.⁹⁵ 

Anti-Obesity Effects

The main characteristic secondary metabolites of Rhaponticum are ecdysteroids. In order to determine an Rhaponticum’s ecdysteroid profile, a novel, sensitive, and robust high-performance thin-layer chromatography (HPTLC) method was developed and validated. Moreover, a comparative analysis was conducted to investigate the effects of Rhaponticum and its secondary metabolites on adipogenesis and adipolysis. The presence of 20-hydroxyecdysone, and turkesterone in Rhaponticum significantly reduced lipid accumulation in human adipocytes, demonstrating their anti-adipogenic activity. Bottom line, exhibits anti-obesity effects by reducing adipogenesis and promoting lipolysis in human adipocytes.⁹⁹ 

My foundational protocol for metabolic optimization, weigh management and to mitigate the adverse impact of GLP-1 inhibitors consist of:

1. Morning Smoothie recipe with scoop each of an amino acid based anabolic nutrient rich powder blend plus a concentrated organic powder blend of super greens, vegetables, and fruit powder blend.
2. Botanical anabolic adaptogenic day-time formula featuring Rhaponticum carthamoides, Epimedium spp, Shilajit, also known as Mumie, and Cissus quadrangularis.
3. Botanical anabolic night-time anabolic endocrine restorative formula featuring, Eurycoma jack, Tribulus terrestris, Mucuna puriens, Maca, the amino acid citrulline, and the natural aromatase reducer, Chrysin.
4. Insulin and glucose nutrient/botanical sensitizing formula blend featuring Bitter melon (Momordica charantia), Pterocarpus marsupium, Salacia reticulata, Cinnamon Bark, and key nutrients such as lipoic acid, chromium, vanadium etc. 
5. Naturized vitamin D, together with red palm oil (vitamin A), and Vitamin K.
6. Weight Management Tea blend from the Mederi center (drink 2-4 cups daily) features the following herbs: Green tea, hibiscus, dandelion root and leaf, hawthorn leaf, flower and berry, and cinnamon bark. The addition of a liquid adaptogen tonic formula is also suggested. I suggest 1-2 dropper-fulls into each cup of tea. Adaptogens improve energy transfer (more efficient use of oxygen, sugar and fats for energy), adaptation, help combat stress, and aid in building muscle (anabolic).

Stress Management: A Critical Factor

The connection between stress and GLP-1 function represents a crucial aspect of metabolic health:

1. Stress Impact: Chronic stress and elevated cortisol levels can significantly impair GLP-1 function and insulin sensitivity. This occurs through several mechanisms:

• Activation of the HPA axis
• Increased gut permeability
• Altered bacterial composition in the intestinal environment

2. Breaking the Cycle: High insulin levels contribute to elevated cortisol, which in turn affects glucose and insulin levels, creating a challenging feedback loop. Managing stress through various interventions, including adaptogenic herbs, can help break this cycle and restore hormonal balance.

Understanding the relationship between gut health and GLP-1 provides valuable insights into metabolic health optimization. By focusing on gut microbiome support through diet, stress management, and targeted supplementation, we can naturally enhance GLP-1 function and achieve better metabolic outcomes.

Additional Suggestions:

1. Fiber load before your largest meal: Use whole psyllium seed powder, mix into some water and drink 15-30 minutes before the meal, followed by a glass of the Weight Management Tea, and/or a cup of miso soup.
2. Apple cider vinegar drink mixed with water or even better the Weight Management Tea. Mix together ¼ cup Bragg’s apple cider vinegar, ¼ cup fresh lemon juice, ¼ raw honey, and 1 tsp. of ginger paste/juice. Mix this into a pint of water or tea and put into a mason jar and store in the refrigerator. Drink 4 oz. 1-3x’s daily.
3. Best foods to eat daily include: artichokes, apples, grapefruit (a ½ of a grapefruit is great for a between meal snack), pomegranate, mushrooms (all mushrooms), seaweed (can get seaweed nori snacks for between meals); eggplant, chili peppers, and all melons. Include beans, legumes, whole grains, potatoes, and eggs in your diet as well. Be sure not to fry foods in oil, and although many fats are good for you and keep in mind, they are dense food high in calories. Spices, including mustard, horseradish, ginger, and cayenne pepper. 
4. Physical activity/exercise: I recommend each week to rotate between 3 different exercises; One for should be strength training to build lean muscle mass, the 2nd should include stretching, a focus on flexibility, balance, and breathing, and the 3rd should be endurance/aerobic should as walking (with hills), hiking, biking or swimming. 
5. Circadian clock: Try and get between 7-9 hours a high quality sleep – do not go to bed too late and do not wake up too early. Nighttime is the time our body regenerates and anabolism kicks in, and we also detoxify during the evening as well at the molecular, cellular and organ system levels.

I also recommend you read my blog entitled, “What’s Causing the Alarming Increases in Cancer Among Younger Adults?” https://www.donnieyance.com/whats-causing-the-alarming-increases-in-cancer-among-younger-adults/. I list several other foods that target the hormone leptin and can also aid in reducing body, particularly the white adipose fat, which is primarily used by the body for insulation, to keep us warm, and for preservation during a famine. 

The beautiful thing about understanding cellular health is that it empowers you to make better choices. Every meal becomes an opportunity to nourish your body at the deepest level. You don’t need to make dramatic changes all at once – small, consistent improvements can lead to remarkable results.

Start by adding more colorful foods to your meals. Listen to your body’s needs. Stay hydrated. Move regularly. Rest well. These aren’t just health tips; they’re investments in your cellular well-being.

The Future of Your Health 

Remember, your body is incredibly resilient and adaptable. It’s never too late to start giving it better support. Whether you’re in your 20s or your 70s, your cells are constantly renewing themselves, creating opportunities for better health with each passing day.

Your next meal isn’t just food – it’s information for your cells, instructions for your genes, and building materials for your future self. Make it count. Your body’s amazing chemistry is always working for you; why not give it the best tools for the job?

References

1. Wang JY, Wang QW, Yang XY, Yang W, Li DR, Jin JY, Zhang HC, Zhang XF. GLP-1 receptor agonists for the treatment of obesity: Role as a promising approach. Front Endocrinol (Lausanne). 2023 Feb 1;14:1085799. doi: 10.3389/fendo.2023.1085799.

2. Wang J. Y., Wang Q.-W., Yang X.-Y., et al. GLP-1 receptor agonists for the treatment of obesity: role as a promising approach. Frontiers in Endocrinology. 2023;14 doi: 10.3389/fendo.2023.1085799.1085799

3. Abdullah Bin Ahmed I. A Comprehensive Review on Weight Gain following Discontinuation of Glucagon-Like Peptide-1 Receptor Agonists for Obesity. J Obes. 2024 May 10;2024:8056440. doi: 10.1155/2024/8056440. PMID: 38765635; PMCID: PMC11101251.

4. Raza FA, Altaf R, Bashir T, Asghar F, Altaf R, Tousif S, Goyal A, Mohammed A, Mohammad MF, Anan M, Ali S. Effect of GLP-1 receptor agonists on weight and cardiovascular outcomes: A review. Medicine (Baltimore). 2024 Nov 1;103(44):e40364. doi: 10.1097/MD.0000000000040364. PMID: 39496023; PMCID: PMC11537668.

5. McIntyre, R. S., Mansur, R. B., Rosenblat, J. D., & Kwan, A. T. H. (2023). The association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidality: reports to the Food and Drug Administration Adverse Event Reporting System (FAERS). Expert Opinion on Drug Safety, 23(1), 47–55. https://doi.org/10.1080/14740338.2023.2295397

6. Zhou, J., Zheng, Y., Xu, B. et al. Exploration of the potential association between GLP-1 receptor agonists and suicidal or self-injurious behaviors: a pharmacovigilance study based on the FDA Adverse Event Reporting System database. BMC Med 22, 65 (2024). https://doi.org/10.1186/s12916-024-03274-6

7. Ueda P, Söderling J, Wintzell V, et al. GLP-1 Receptor Agonist Use and Risk of Suicide Death. JAMA Intern Med. 2024;184(11):1301–1312. doi:10.1001/jamainternmed.2024.4369

8. Ussher, J.R., Drucker, D.J. Glucagon-like peptide 1 receptor agonists: cardiovascular benefits and mechanisms of action. Nat Rev Cardiol 20, 463–474 (2023). https://doi.org/10.1038/s41569-023-00849-3

9. Deanfield, John et al. Semaglutide and cardiovascular outcomes by baseline and changes in adiposity measurements: a prespecified analysis of the SELECT trial, The Lancet, Online first, October 22, 2025, Volume 0, Issue 0

10. Nicholls SJ, Ryan DH, Deanfield J, et al. Semaglutide and Hospitalizations in Patients With Obesity and Established Cardiovascular Disease: An Exploratory Analysis of the SELECT Randomized Clinical Trial. JAMA Cardiol. Published online December 23, 2025. doi:10.1001/jamacardio.2025.4824

11. Linge J, Birkenfeld AL, Neeland IJ. Muscle Mass and Glucagon-Like Peptide-1 Receptor Agonists: Adaptive or Maladaptive Response to Weight Loss? Circulation. 2024 Oct 15;150(16):1288-1298. doi: 10.1161/CIRCULATIONAHA.124.067676. Epub 2024 Oct 14. PMID: 39401279.

12. Expert Tips for Managing GLP-1 Medication Side Effects – Medscape – December 27, 2024.

13. Yeo, Yee HuiGaddam, SrinivasNg, Wee HanHuang, Pin-ChiaMohamed, GhadaMa, Kevin Sheng-KaiRezaie, Ali et al. Increased Risk of Aspiration Pneumonia Associated With Endoscopic Procedures Among Patients With Glucagon-like Peptide 1 Receptor Agonist Use. Gastroenterology, Volume 167, Issue 2, 402 – 404.e3

14. Carla M Prado et al, Muscle matters: the effects of medically induced weight loss on skeletal muscle, The Lancet Diabetes & Endocrinology (2024). DOI: 10.1016/S2213-8587(24)00272-9

15. Clinicaloptions.com, Prado CM, Landi F, Chew STH, Atherton PJ, Molinger J, Ruck T, Gonzalez MC. Advances in muscle health and nutrition: A toolkit for healthcare professionals. Clin Nutr. 2022 Oct;41(10):2244-2263. doi: 10.1016/j.clnu.2022.07.041. Epub 2022 Aug 7. PMID: 36081299.

16. Karasawa, Takuya et al. Unexpected effects of semaglutide on skeletal muscle mass and force-generating capacity in mice, Cell Metabolism (2025). DOI: 10.1016/j.cmet.2025.07.004. www.cell.com/cell-metabolism/f … 1550-4131(25)00331-6

17. Unseen Cost of Weight Loss and Aging: Tackling Sarcopenia – Medscape – October 16, 2024.

18. Matthew D. Martens et al, Semaglutide Reduces Cardiomyocyte Size and Cardiac Mass in Lean and Obese Mice, JACC: Basic to Translational Science (2024). DOI: 4/510.1016/j.jacbts.2024.07.006

19. Medscape, Mary Brophy Marcus, January 19, 2026, https://www.medscape.com/viewarticle/scary-health-risk-can-sneak-glp-1-users-2026a10001pi; Spreckley M, Ruggiero CF, Brown A. Nutrition Strategies for Next-Generation Incretin Therapies: A Systematic Scoping Review of the Current Evidence. Obes Rev. 2026 Jan 7:e70079. doi: 10.1111/obr.70079. Epub ahead of print. PMID: 41500509.

20. Should Patients With Thyroid Issues Take GLP-1s? It Depends – Medscape – December 19, 2024.

21. He L, Wang J, Ping F, et al. Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases: A Systematic Review and Meta-analysis of Randomized Clinical Trials. JAMA Intern Med. 2022;182(5):513–519. doi:10.1001/jamainternmed.2022.0338

22. Sodhi M, Rezaeianzadeh R, Kezouh A, Etminan M. Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss. JAMA. 2023;330(18):1795–1797. doi:10.1001/jama.2023.19574

23. PRAC concludes eye condition NAION is a very rare side effect of semaglutide medicines, Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 2-5 June 2025, 6 June 2025

24. Hathaway JT, Shah MP, Hathaway DB, et al. Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide. JAMA Ophthalmol. 2024;142(8):732–739. doi:10.1001/jamaophthalmol.2024.2296

25. Study details from Canadian health center retrospective analysis. Data presented November 2025. Full citation pending publication in peer-reviewed cardiovascular journal. Edited by Archita Rai, November 26, 2025, Medscape, https://www.medscape.com/viewarticle/glp-1s-pose-heart-risks-patients-hfref-and-implants-2025a1000x1d?ecd=mdedge_sum

26. Gallagher TJ, Razura DE, Li A, Kim I, Vukkadala N, Barbu AM. Glucagon-Like Peptide-1 Receptor Agonists and Chronic Cough. JAMA Otolaryngol Head Neck Surg. Published online November 26, 2025. doi:10.1001/jamaoto.2025.4181

27. Henderson, Jennifer Enterprise & Investigative Writer, MedPage Today, July 22, 2025

28. Zhong, Y., Wu, T. & Khan, N.U. Association between GLP-1 receptor agonists as a class and colorectal cancer risk: a meta-analysis of retrospective cohort studies. BMC Gastroenterol 25, 614 (2025). https://doi.org/10.1186/s12876-025-04211-4

29. Dai H, Li Y, Lee YA, et al. GLP-1 Receptor Agonists and Cancer Risk in Adults With Obesity. JAMA Oncol. Published online August 21, 2025. doi:10.1001/jamaoncol.2025.2681

3o. Freeman, S. (2025, September 17). Telogen Effluvium and Androgenic Alopecia Rates High Among GLP-1 Receptor Agonist Users. Medscape Medical News. Retrieved from https://www.medscape.com/viewarticle/telogen-effluvium-and-androgenic-alopecia-rates-high-among-2025a1000oo9

31. Maya J, Pant D, Fu Y, James K, Batlle C, Hsu S, Soria-Contreras DC, Shook LL, Mow C, Hivert MF, Thaweethai T, Powe CE. Gestational Weight Gain and Pregnancy Outcomes After GLP-1 Receptor Agonist Discontinuation. JAMA. 2025 Nov 24:e2520951. doi: 10.1001/jama.2025.20951. Epub ahead of print. PMID: 41284263; PMCID: PMC12645404.

32. Sjöström L., Rissanen A., Andersen T., et al. Randomised plaebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. The Lancet. 1998;352(9123):167–172. doi: 10.1016/s0140-6736(97)11509-4.

33. (PDF) A Comprehensive Review on Weight Gain following Discontinuation of Glucagon-Like Peptide-1 Receptor Agonists for Obesity. Available from: https://www.researchgate.net/publication/380516821_A_Comprehensive_Review_on_Weight_Gain_following_Discontinuation_of_Glucagon-Like_Peptide-1_Receptor_Agonists_for_Obesity accessed Nov 27 2024.

34. Lopez-Jimenez F., Almahmeed W., Bays H., et al. Obesity and cardiovascular disease: mechanistic insights and management strategies. A joint position paper by the World Heart Federation and World Obesity Federation. European Journal of Preventive Cardiology. 2022;29(17):2218–2237. doi: 10.1093/eurjpc/zwac187.

35. Paschalis Karakasis, Dimitrios Patoulias, Nikolaos Fragakis, Christos S. Mantzoros, Effect of glucagon-like peptide-1 receptor agonists and co-agonists on body composition: Systematic review and network meta-analysis, Metabolism, 164, (156113), (2025).

36. Abdisa KB, Szerdahelyi E, Molnár MA, Friedrich L, Lakner Z, Koris A, Toth A, Nath A. Metabolic Syndrome and Biotherapeutic Activity of Dairy (Cow and Buffalo) Milk Proteins and Peptides: Fast Food-Induced Obesity Perspective-A Narrative Review. Biomolecules. 2024 Apr 14;14(4):478. doi: 10.3390/biom14040478. 

37. Abdisa KB, Szerdahelyi E, Molnár MA, Friedrich L, Lakner Z, Koris A, Toth A, Nath A. Metabolic Syndrome and Biotherapeutic Activity of Dairy (Cow and Buffalo) Milk Proteins and Peptides: Fast Food-Induced Obesity Perspective-A Narrative Review. Biomolecules. 2024 Apr 14;14(4):478. doi: 10.3390/biom14040478. (self-developed, concept was adopted from Ussar et al., 2016

38. https://courses.lumenlearning.com/suny-ap2/chapter/overview-of-metabolic-reactions/

39. Prado CM, Landi F, Chew STH, Atherton PJ, Molinger J, Ruck T, Gonzalez MC. Advances in muscle health and nutrition: A toolkit for healthcare professionals. Clin Nutr. 2022 Oct;41(10):2244-2263. doi: 10.1016/j.clnu.2022.07.041. Epub 2022 Aug 7. PMID: 36081299.

40. Berryman, C. E., Lieberman, H. R., Fulgoni, V. L., & Pasiakos, S. M. (2018). Protein intake trends and conformity with the Dietary Reference Intakes in the United States: Analysis of the National Health and Nutrition Examination Survey, 2001-2014. The American Journal of Clinical Nutrition, 108(2), 405–413. https://doi.org/10.1093/ajcn/nqy088

41. Berryman, C. E., Lieberman, H. R., Fulgoni, V. L., & Pasiakos, S. M. (2018). Protein intake trends and conformity with the Dietary Reference Intakes in the United States: Analysis of the National Health and Nutrition Examination Survey, 2001-2014. The American Journal of Clinical Nutrition, 108(2), 405–413. https://doi.org/10.1093/ajcn/nqy088https://doi.org/10.1093/ajcn/nqy088

42. Traylor, D. A., Gorissen, S. H. M., & Phillips, S. M. (2018). Perspective: Protein Requirements and Optimal Intakes in Aging: Are We Ready to Recommend More Than the Recommended Daily Allowance? Advances in Nutrition (Bethesda, Md.), 9(3), 171–182. https://doi.org/10.1093/advances/nmy003

43. Harvard T.H. Chan School of Public Health. (n.d.). Protein. Retrieved from https://www.hsph.harvard.edu/nutritionsource/what-should-you-eat/protein/#protein-research

44. Fernando Naclerio, Marcos Seijo, Whey protein supplementation and muscle mass: current perspectives, Pages 37-48 | Published online: 29 Aug 2019,, https://doi.org/10.2147/NDS.S166195

45. Farvid, M. S., Cho, E., Chen, W. Y., Eliassen, A. H., & Willett, W. C. (2015). Adolescent meat intake and breast cancer risk. International Journal of Cancer, 136(8), 1909–1920. https://doi.org/10.1002/ijc.29218

46. Morton RW, Murphy KT, McKellar SR, Schoenfeld BJ, Henselmans M, Helms E, Aragon AA, Devries MC, Banfield L, Krieger JW, Phillips SM. A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults. Br J Sports Med. 2018 Mar;52(6):376-384. doi: 10.1136/bjsports-2017-097608. Epub 2017 Jul 11. Erratum in: Br J Sports Med. 2020 Oct;54(19):e7. PMID: 28698222; PMCID: PMC5867436.

47. Margolis LM, Rivas DA. Implications of exercise training and distribution of protein intake on molecular processes regulating skeletal muscle plasticity. Calcif Tissue Int. 2015 Mar;96(3):211-21. doi: 10.1007/s00223-014-9921-0. Epub 2014 Oct 28. PMID: 25348078; PMCID: PMC6691734.

48. Sousa GT, Lira FS, Rosa JC, de Oliveira EP, Oyama LM, Santos RV, Pimentel GD. Dietary whey protein lessens several risk factors for metabolic diseases: a review. Lipids Health Dis. 2012 Jul 10;11:67. doi: 10.1186/1476-511X-11-67.

49. Frestedt JL, Zenk JL, Kuskowski MA, Ward LS, Bastian ED. A whey-protein supplement increases fat loss and spares lean muscle in obese subjects: a randomized human clinical study. Nutr Metab (Lond) 2008;5:8. doi: 10.1186/1743-7075-5-8.

50. Devries MC, Phillips SM. Supplemental protein in support of muscle mass and health: advantage whey. J Food Sci. 2015 Mar;80 Suppl 1:A8-A15. doi: 10.1111/1750-3841.12802.

51. Sindayikengera S, Xia WS. Nutritional evaluation of caseins and whey proteins and their hydrolysates from Protamex. J Zhejiang Univ Sci B. 2006 Feb;7(2):90-8. doi: 10.1631/jzus.2006.B0090.

52. Gottlob RO, DeRouchey JM, Tokach MD, Goodband RD, Dritz SS, Nelssen JL, Hastad CW, Knabe DA. Amino acid and energy digestibility of protein sources for growing pigs. J Anim Sci. 2006 Jun;84(6):1396-402.

53. Sousa GT, Lira FS, Rosa JC, de Oliveira EP, Oyama LM, Santos RV, Pimentel GD. Dietary whey protein lessens several risk factors for metabolic diseases: a review. Lipids Health Dis. 2012 Jul 10;11:67. doi: 10.1186/1476-511X-11-67.

54. Sepandi M, Samadi M, Shirvani H, Alimohamadi Y, Taghdir M, Goudarzi F, Akbarzadeh I. Effect of whey protein supplementation on weight and body composition indicators: A meta-analysis of randomized clinical trials. Clin Nutr ESPEN. 2022 Aug;50:74-83. doi: 10.1016/j.clnesp.2022.05.020. Epub 2022 Jun 6.

55. Davies RW, Carson BP, Jakeman PM. The Effect of Whey Protein Supplementation on the Temporal Recovery of Muscle Function Following Resistance Training: A Systematic Review and Meta-Analysis. Nutrients. 2018 Feb 16;10(2):221. doi: 10.3390/nu10020221.

56. Li ML, Zhang F, Luo HY, Quan ZW, Wang YF, Huang LT, Wang JH. Improving sarcopenia in older adults: a systematic review and meta-analysis of randomized controlled trials of whey protein supplementation with or without resistance training. J Nutr Health Aging. 2024 Apr;28(4):100184. doi: 10.1016/j.jnha.2024.100184. Epub 2024 Feb 12.

57. Franceschelli A, Cappello A, Cappello G. Retrospective study on the effects of a whey protein concentrate on body composition in 262 sarcopenic tube fed patients. Minerva Med. 2013 Feb;104(1):103-112.

58. Royle PJ, McIntosh GH, Clifton PM. Whey protein isolate and glycomacropeptide decrease weight gain and alter body composition in male Wistar rats. Br J Nutr. 2008 Jul;100(1):88-93. doi: 10.1017/S0007114507883000.

59. Wilson GJ, Wilson JM, Manninen AH. Effects of beta-hydroxy-beta-methylbutyrate (HMB) on exercise performance and body composition across varying levels of age, sex, and training experience: a review. Nutr Metab. 2008;5:1.

60. Nissen SL, Abumrad NN. Nutritional role of the leucine metabolite β-hydroxy β-methylbutyrate (HMB). J Nutr Biochem. 1997;8:300-311.

61. Eley HL, Russell ST, Tisdale MJ. Attenuation of depression of muscle protein synthesis induced by lipopolysaccharide, tumor necrosis factor, and angiotensin II by β-hydroxy-β-methylbutyrate. Am J Physiol Endocrinol Metab. 2008;295:E1409-E1416

62. Candow DG, Chilibeck PD, Forbes SC, Fairman CM, Gualano B, Roschel H. Creatine supplementation for older adults: Focus on sarcopenia, osteoporosis, frailty and Cachexia. Bone. 2022 Sep;162:116467. doi: 10.1016/j.bone.2022.116467.

63. Smith-Ryan AE, Cabre HE, Eckerson JM, Candow DG. Creatine Supplementation in Women’s Health: A Lifespan Perspective. Nutrients. 2021 Mar 8;13(3):877. doi: 10.3390/nu13030877.

64. Bredahl EC, Hydock DS. Creatine Supplementation and Doxorubicin-Induced Skeletal Muscle Dysfunction: An Ex Vivo Investigation. Nutr Cancer. 2017 May-Jun;69(4):607-615. doi: 10.1080/01635581.2017.1295089

65. Kuhn KS, Muscaritoli M, Wischmeyer P, Stehle P. Glutamine as indispensable nutrient in oncology: experimental and clinical evidence, Eur J Nutr. 2009 Nov 21.

66. Dos Santos K, Bertho G, Baudin M, Giraud N. Glutamine: A key player in human metabolism as revealed by hyperpolarized magnetic resonance. Prog Nucl Magn Reson Spectrosc. 2024 Nov-Dec;144-145:15-39. doi: 10.1016/j.pnmrs.2024.05.003.

67. Sadaf A, Quinn CT. L-glutamine for sickle cell disease: Knight or pawn? Exp Biol Med (Maywood). 2020 Jan;245(2):146-154. doi: 10.1177/1535370219900637. Epub 2020 Jan 27. PMID: 31985279; PMCID: PMC7016414.

68. Antonio J, Street C. Glutamine: a potentially useful supplement for athletes. Can J Appl Physiol. 1999;24:1-14.

69. MacLennan PA, Smith K, Weryk B, Watt PW, Rennie MJ. Inhibition of protein breakdown by glutamine in perfused rat skeletal muscle. FEBS Lett. 1988;237:133-6.

70. Almeida EB, Santos JMB, Paixão V, Amaral JB, Foster R, Sperandio A, Roseira T, Rossi M, Cordeiro TG, Monteiro FR, Amirato GR, Santos CAF, Vieira RP, Vaisberg M, Barros MP, Bachi ALL. L-Glutamine Supplementation Improves the Benefits of Combined-Exercise Training on Oral Redox Balance and Inflammatory Status in Elderly Individuals. Oxid Med Cell Longev. 2020 Jan 22;2020:2852181. doi: 10.1155/2020/2852181.

71. Laviano A, Molfino A, Lacaria MT, Canelli A, De Leo S, Preziosa I, Rossi Fanelli F. Glutamine supplementation favors weight loss in nondieting obese female patients. A pilot study. Eur J Clin Nutr. 2014 Nov;68(11):1264-6. doi: 10.1038/ejcn.2014.184.

72. Breuillard C., Cynober L., Moinard C. Citrulline and nitrogen homeostasis: An overview. Amino Acids. 2015;47:685–691. doi: 10.1007/s00726-015-1932-2. 

73. Gonzalez AM, Townsend JR, Pinzone AG, Hoffman JR. Supplementation with Nitric Oxide Precursors for Strength Performance: A Review of the Current Literature. Nutrients. 2023 Jan 28;15(3):660. doi: 10.3390/nu15030660.

74. Xie S, Li S, Shaharudin S. The Effects of Combined Exercise with Citrulline Supplementation on Body Composition and Lower Limb Function of Overweight Older Adults: A Systematic Review and Meta-Analysis. J Sports Sci Med. 2023 Sep 1;22(3):541-548. doi: 10.52082/jssm.2023.541. PMID: 37711701; PMCID: PMC10499154.

75. Flores-Ramírez AG, Tovar-Villegas VI, Maharaj A, Garay-Sevilla ME, Figueroa A. Effects of L-Citrulline Supplementation and Aerobic Training on Vascular Function in Individuals with Obesity across the Lifespan. Nutrients. 2021 Aug 27;13(9):2991. doi: 10.3390/nu13092991.

76. Romero MJ, Platt DH, Caldwell RB, Caldwell RW. Therapeutic use of citrulline in cardiovascular disease. Cardiovasc Drug Rev 2006; 24: 275–290.

77. Koeners MP, van Faassen EE, Wesseling S, de Sain-van der Velden M, Koomans HA, Braam B, Joles JA. Maternal supplementation with citrulline increases renal nitric oxide in young spontaneously hypertensive rats and has long-term antihypertensive effects. Hypertension 2007; 50: 1077–1084.

78. Wu G, Collins JK, Perkins-Veazie P, Siddiq M, Dolan KD, Kelly KA, Heaps CL, Meininger CJ. Dietary supplementation with watermelon pomace juice enhances arginine availability and ameliorates the metabolic syndrome in Zucker diabetic fatty rats. J Nutr 2007; 137: 2680–2685.

79. Schwedhelm E, Maas R, Freese R, Jung D, Lukacs Z, Jambrecina A, Spickler W, Schulze F, BoÅNger RH. Pharmacokinetic and pharmacodynamic properties of oral l-citrulline and l-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol 2008; 65: 51–59.

80. Figueroa A, Trivino JA, Sanchez-Gonzalez MA, Vicil F. Oral L-citrulline supplementation attenuates blood pressure response to cold pressor test in young men. Am J Hypertens. 2010 Jan;23(1):12-6. Epub 2009 Oct 22.

81. Gkekas NK, Anagnostis P, Paraschou V, Stamiris D, Dellis S, Kenanidis E, et al. The effect of vitamin D plus protein supplementation on sarcopenia: a systematic review and meta-analysis of randomized controlled trials. Maturitas 2021;145:56e63.

82. Latham CM, Brightwell CR, Keeble AR, Munson BD, Thomas NT, Zagzoog AM, Fry CS, Fry JL. Vitamin D Promotes Skeletal Muscle Regeneration and Mitochondrial Health. Front Physiol. 2021 Apr 14;12:660498. doi: 10.3389/fphys.2021.660498. PMID: 33935807; PMCID: PMC8079814.

83. Prado CM, Landi F, Chew STH, Atherton PJ, Molinger J, Ruck T, Gonzalez MC. Advances in muscle health and nutrition: A toolkit for healthcare professionals. Clin Nutr. 2022 Oct;41(10):2244-2263. doi: 10.1016/j.clnu.2022.07.041. Epub 2022 Aug 7. PMID: 36081299.

84. Latham CM, Brightwell CR, Keeble AR, Munson BD, Thomas NT, Zagzoog AM, Fry CS, Fry JL. Vitamin D Promotes Skeletal Muscle Regeneration and Mitochondrial Health. Front Physiol. 2021 Apr 14;12:660498. doi: 10.3389/fphys.2021.660498. PMID: 33935807; PMCID: PMC8079814.

85. Choi M, Park H, Cho S, Lee M. Vitamin D3 supplementation modulates inflammatory responses from the muscle damage induced by high-intensity exercise in SD rats. Cytokine 2013;63(1):27e35.

86. Prietl B, Pilz S, Wolf M, Tomaschitz A, Obermayer-Pietsch B, Graninger W, et al. Vitamin D supplementation and regulatory T cells in apparently healthy subjects: vitamin D treatment for autoimmune diseases? Isr Med Assoc J 2010;12(3):136e9.

87. Dzik, K.P., Kaczor, J.J. Mechanisms of vitamin D on skeletal muscle function: oxidative stress, energy metabolism and anabolic state. Eur J Appl Physiol 119, 825–839 (2019). https://doi.org/10.1007/s00421-019-04104-x

88. Rice AL, Burns JB. Moving from efficacy to effectiveness: red palm oil’s role in preventing vitamin A deficiency. J Am Coll Nutr. 2010 Jun;29(3 Suppl):302S-313S. doi: 10.1080/07315724.2010.10719845. PMID: 20823490

89. Dong S, Xia H, Wang F, Sun G. The Effect of Red Palm Oil on Vitamin A Deficiency: A Meta-Analysis of Randomized Controlled Trials. Nutrients. 2017 Nov 24;9(12):1281. doi: 10.3390/nu9121281. PMID: 29186779; PMCID: PMC5748732.

90. Kokoskaa L, Janovskab D. Chemistry and pharmacology of Rhaponticum carthamoides: A review. Phytochemistry. May 2009. Vol 70, Issue 7:842- 855.

91. Baltaev U, Abubakirov NK. Phytoecdysteroids. Rhaponticum carthamoides. Chemistry of Natural Compounds. 1987. 5: 681-684.

92. Varga E, Szendrei K, et al. Study of the compounds contained Hungarian-grown Leuzea carthamoides with special regard to the ecdysteroids. Herba Hungarica. 1986. 25(1): 115-127.

93. Bathori, M.; Toth, N.; Hunyadi, A.; Marki, A.; Zador, E. Phytoecdysteroids and anabolic-androgenic steroids—Structure and effects on humans. Curr. Med. Chem. 2008, 15, 75–91.

94. Kokoskaa L, Janovskab D. Chemistry and pharmacology of Rhaponticum carthamoides: A review. Phytochemistry. May 2009. Vol 70, Issue 7:842-855.

95. Todorova V, Ivanov K, Ivanova S. Comparison between the Biological Active Compounds in Plants with Adaptogenic Properties (Rhaponticum carthamoides, Lepidium meyenii, Eleutherococcus senticosus and Panax ginseng). Plants (Basel). 2021 Dec 26;11(1):64. doi: 10.3390/plants11010064. PMID: 35009068; PMCID: PMC8747685.

 96. Todorova V, Ivanova S, Chakarov D, Kraev K, Ivanov K. Ecdysterone and Turkesterone-Compounds with Prominent Potential in Sport and Healthy Nutrition. Nutrients. 2024 May 2;16(9):1382. doi: 10.3390/nu16091382. PMID: 38732627; PMCID: PMC11085066.

97. Zihan Zheng, Yushan Xian, Zhen Jin, Feng Yao, YiZhen Liu, Ying Deng, Bo Wang, Danli Chen, Jianjun Yang, Lingxuan Ren, Rong Lin,Rhaponticum carthamoides improved energy metabolism and oxidative stress through the SIRT6/Nrf2 pathway to ameliorate myocardial injury, Phytomedicine, Volume 105, 2022, 154197, ISSN 0944-7113, https://doi.org/10.1016/j.phymed.2022.154197. (https://www.sciencedirect.com/science/article/pii/S0944711322002756)

98. Syrov VN, Shakhmurova GA, Khushbaktova ZA. Effects of phytoecdysteroids and bemithyl on functional, metabolic, and immunobiological parameters of working capacity in experimental animals. Eksp Klin Farmakol. 2008 Sep-Oct;71(5):40-3.

99. Todorova V, Savova MS, Ivanova S, Ivanov K, Georgiev MI. Anti-Adipogenic Activity of Rhaponticum carthamoides and Its Secondary Metabolites. Nutrients. 2023 Jul 7;15(13):3061. doi: 10.3390/nu15133061.