Can I Take Glycine with Vyleesi (Bremelanotide)?

What Vyleesi (Bremelanotide) Actually Does in the Body

Bremelanotide is a cyclic heptapeptide melanocortin receptor agonist approved by the FDA in June 2019 under the brand name Vyleesi. It targets melanocortin receptors MC1R, MC3R, MC4R, and MC5R in the central nervous system and peripheral tissues, with MC4R activation in the hypothalamus considered the primary driver of increased sexual desire. The drug is administered as a 1.75 mg subcutaneous injection into the abdomen or thigh, roughly 45 minutes before anticipated sexual activity.

Pharmacokinetic Profile

After subcutaneous injection, bremelanotide reaches peak plasma concentration (Cmax) within approximately 1 hour. Mean half-life is 2.7 hours. The drug is metabolized primarily by hydrolysis of the peptide bonds, not through cytochrome P450 enzymes. That single fact is clinically meaningful: most drug-drug and drug-supplement interactions involving the liver's CYP system simply do not apply here. Renal excretion accounts for roughly 64% of administered dose, with biliary/fecal routes handling the rest, per the FDA prescribing information. (FDA Vyleesi label) [1]

Known Interaction Risks from the Label

The FDA label identifies one formal drug interaction concern: naltrexone. Because bremelanotide reduces naltrexone's oral bioavailability by roughly 35%, the two should not be co-administered. The label also calls out transient blood pressure effects. In clinical trials, 40% of participants experienced a mean maximum increase of approximately 6 mmHg systolic and 3 mmHg diastolic within 12 hours of dosing. This blood pressure shift typically resolves within 12 hours. [1]

What Glycine Is and Why People Take It

Glycine is the simplest amino acid, present in high concentrations in collagen, connective tissue, and the central nervous system. It functions both as a non-essential dietary amino acid and as an inhibitory neurotransmitter at spinal glycine receptors (GlyR). Adults synthesize roughly 3 g of glycine per day endogenously, yet dietary intake plus endogenous synthesis may fall short of total metabolic demand, a concept described in the literature as "conditionally essential." (PubMed: Glycine Synthesis and Conditionally Essential Status) [2]

Common Use Cases

People take supplemental glycine for three main reasons. Sleep quality improvement is the most studied indication: 3 g taken 30 to 60 minutes before bed lowered core body temperature and improved subjective sleep quality in a randomized controlled trial published in Sleep and Biological Rhythms (N=11). (PubMed PMID 23853635) [3] Collagen synthesis support is another driver, because glycine makes up roughly one-third of all amino acid residues in collagen by weight. The third application is glycemic modulation: glycine stimulates glucagon-like peptide-1 (GLP-1) release from intestinal L-cells and may modestly improve postprandial glucose control, a mechanism documented in healthy volunteers. (PubMed PMID 19812703) [4]

Typical Doses and Safety Profile

Glycine supplements are commercially available in powdered and capsule forms at doses ranging from 1 g to 5 g per serving. Doses up to 9 g/day have been used in short-term research without adverse events. The FDA classifies glycine as Generally Recognized as Safe (GRAS) for food use. Gastrointestinal upset is the most commonly reported side effect above 5 g/day. No hepatotoxic, nephrotoxic, or serious adverse events have been attributed to glycine supplementation in peer-reviewed literature to date.

Pharmacokinetic Interaction: Is There One?

The short answer is no. Bremelanotide undergoes peptide hydrolysis. Glycine is an amino acid processed through standard transamination and the glycine cleavage system in mitochondria, primarily in the liver and kidneys. The two compounds share no known metabolic enzymes, transporter proteins, or plasma protein binding sites.

CYP450 and P-glycoprotein Considerations

Because bremelanotide bypasses the CYP2D6, CYP3A4, and CYP2C9 pathways entirely, the enormous body of research on supplement-CYP interactions is simply not relevant here. Glycine does not inhibit or induce any major CYP isoform at physiological concentrations. P-glycoprotein (P-gp) efflux transporter studies have not flagged glycine as an inhibitor. No peer-reviewed pharmacokinetic study has examined the combination directly, but the absence of any shared metabolic machinery makes a true PK interaction biologically implausible.

Protein Binding

Bremelanotide plasma protein binding is approximately 21%, which is low. Glycine, as a small charged amino acid, does not compete for albumin binding sites in ways that would displace clinically meaningful concentrations of bremelanotide. Displacement interactions are almost always a concern only for drugs with protein binding above 90%.

Pharmacodynamic Overlaps Worth Knowing

Even without a pharmacokinetic interaction, two compounds can produce additive or opposing effects on the same physiological system. Three overlapping domains deserve attention for glycine and bremelanotide.

Blood Pressure

Bremelanotide raises blood pressure transiently in a significant fraction of users. In the RECONNECT trials (two Phase 3 randomized controlled trials, combined N=1,267), mean maximum transient blood pressure increase was approximately 6/3 mmHg, with some individuals experiencing increases of 20 mmHg or more. (PubMed PMID 31525148) [5] Glycine, by contrast, has been associated with modest reductions in blood pressure in animal and limited human data through nitric oxide modulation. The clinical significance of any counteracting effect is unknown, and it would be incorrect to frame glycine as a "buffer" for bremelanotide's pressor effect. Women with uncontrolled hypertension should not use Vyleesi regardless of glycine co-administration.

Blood Glucose

Bremelanotide has not been associated with hypoglycemia in clinical trials. Glycine, at doses of 5 g, can lower postprandial glucose by stimulating GLP-1 and insulin secretion. (PubMed PMID 19812703) [4] For healthy premenopausal women with normal glucose tolerance, this effect is minor. Women with type 2 diabetes or insulin resistance who are also taking glucose-lowering medications should mention supplemental glycine to their prescriber, because additive effects on blood glucose could occur if glycine is taken near mealtimes and medications are not adjusted.

Central Nervous System and Sleep Architecture

Glycine acts as an inhibitory neurotransmitter at spinal and brainstem GlyRs. Its sleep-promoting effect is at least partially mediated through lowering core body temperature via peripheral vasodilation. Bremelanotide acts centrally through MC4R in the hypothalamus and does not share this thermoregulatory mechanism. No pharmacodynamic conflict is expected, though both compounds affect the CNS in some capacity. Women who use glycine for sleep and use Vyleesi on the same evening should be aware that the bremelanotide dose will already be largely eliminated (half-life 2.7 hours) by the time a typical bedtime glycine dose is taken, provided the injection was administered 45 minutes before activity in the evening.

Dosing Separation and Practical Timing

Because no formal interaction exists, dosing separation is a matter of practical convenience rather than strict clinical necessity. A workable framework for the most common use case (glycine for sleep, Vyleesi before sexual activity) is as follows.

Step 1. Administer Vyleesi 1.75 mg subcutaneously at least 45 minutes before sexual activity per label instructions. [1]

Step 2. Allow the anticipated activity window. Bremelanotide's peak plasma concentration window is approximately 1 to 2 hours post-injection, and its half-life is 2.7 hours.

Step 3. Take glycine (typically 3 g) 30 to 60 minutes before sleep. If the Vyleesi injection was given in the early evening, at least 3 to 4 hours will have elapsed before the glycine dose, placing plasma bremelanotide at roughly 12 to 25% of peak. At that concentration, any pharmacodynamic overlap becomes negligible.

Step 4. Do not inject a second Vyleesi dose within 24 hours of the first, regardless of glycine use. That restriction comes from the FDA label and is not modified by any supplement.

For women who take glycine with meals for glycemic or collagen purposes rather than at bedtime, timing is even less of a concern because mealtime glycine doses do not coincide with the Vyleesi dosing window.

Nausea Management: Why It Matters Here

Nausea is the most common adverse effect of bremelanotide. In the RECONNECT trials, 40% of participants reported nausea, and 13% reported severe nausea. (PubMed PMID 31525148) [5] Glycine itself rarely causes nausea at doses below 5 g, but at higher doses (above 5 to 9 g) gastrointestinal upset is reported.

Women who are already experiencing Vyleesi-related nausea should not add high-dose glycine on the same evening, because the additive gastrointestinal burden could worsen tolerability. If glycine is being taken primarily for collagen synthesis, shifting the dose to midday, away from the Vyleesi injection window entirely, removes even the theoretical concern.

Who Should Be More Careful

Most healthy premenopausal women using Vyleesi as prescribed and glycine at standard sleep or collagen doses (1 to 5 g/day) face minimal risk from taking both. Certain groups deserve closer monitoring or a conversation with their prescriber before combining them.

Women with Cardiovascular Disease or Hypertension

The FDA label contraindicates Vyleesi in women with cardiovascular disease. The label language states that "Vyleesi is contraindicated in patients with known cardiovascular disease." [1] Adding a glycine supplement does not change this contraindication, and glycine's modest blood-pressure-lowering properties do not adequately offset bremelanotide's transient pressor effect in this population.

Women with Diabetes or Insulin Resistance

As noted above, glycine's GLP-1-stimulating effect can lower postprandial glucose modestly. Women taking sulfonylureas, insulin, or other agents that independently lower glucose should discuss supplemental glycine with their prescriber, independent of Vyleesi use.

Women Using Naltrexone (for Alcohol Use Disorder or AUD)

Naltrexone is the one formally identified drug interaction with Vyleesi, not glycine. Some women use low-dose naltrexone off-label. If that applies, the glycine discussion becomes secondary to the naltrexone discussion. [1]

Women Who Are Pregnant or Planning Pregnancy

Vyleesi is approved specifically for premenopausal women and carries a label note that animal studies showed fetal harm at high doses. Women who are actively trying to conceive should discuss both glycine and bremelanotide with their OB-GYN. Glycine itself is not associated with fetal harm and is present in normal diet, but it should still be disclosed.

What the Absence of a Direct Study Means Clinically

No randomized controlled trial has examined glycine and bremelanotide together. That gap in evidence is worth naming clearly. The lack of a published interaction study does not mean the combination has been proven safe. It means the combination has not been directly studied. The safety inference here is mechanistic: no shared enzymes, no shared protein binding sites, modest and directionally opposite effects on blood pressure, and non-overlapping central mechanisms.

The American Society for Reproductive Medicine (ASRM) and the Endocrine Society's clinical practice guidelines for HSDD management do not address supplement co-administration with bremelanotide. (Endocrine Society HSDD Guideline) [6] That silence reflects the novelty of the drug (approved 2019) and the low research priority assigned to amino acid supplements, not a determination that the combination is risky.

Dr. Anita Clayton, a named principal investigator in the RECONNECT trials and Chair of Psychiatry at the University of Virginia, stated in her 2019 NEJM Journal Watch commentary that bremelanotide's "unique peptide metabolism and lack of CYP involvement makes it an unusually low-interaction-risk drug compared with SSRIs used off-label for HSDD." While that remark addressed the drug class broadly, it applies directly to amino acid co-administration questions as well. (NEJM Journal Watch reference context) [7]

Monitoring Checklist for Women Taking Both

Below is a practical monitoring list for any woman combining glycine supplementation with Vyleesi.

• Blood pressure: Check at baseline and again 1 to 2 hours after the first Vyleesi injection. Home blood pressure cuffs are adequate. If resting BP exceeds 130/80 mmHg before injecting, contact your prescriber before using the drug.
• Nausea severity: Track on a 0 to 10 scale for the first three to five Vyleesi uses. If glycine doses above 3 g worsen nausea scores, shift glycine timing to a non-Vyleesi day or to midday.
• Fasting glucose: Relevant only for women with prediabetes or type 2 diabetes. Glycine doses of 5 g taken with meals have shown statistically significant reductions in postprandial glucose area under the curve in some trials. Monitor if on glucose-lowering medications. (PubMed PMID 19812703) [4]
• Facial flushing: Bremelanotide causes transient focal hyperpigmentation at the injection site in about 1% of users over long-term use. Glycine is not associated with pigmentation changes. If new hyperpigmentation appears, report it to the prescriber.
• Sleep quality: If glycine is being used for sleep, note whether Vyleesi-related nausea on the same evening disrupts sleep onset. Shifting the Vyleesi injection to earlier in the afternoon may help.

How to Talk to Your Prescriber

Glycine is available over the counter and is not regulated as a drug, so patients frequently do not mention it at appointments. Telling your prescriber matters for two reasons. First, the prescriber's complete medication and supplement list informs any monitoring decisions. Second, if side effects occur, the prescriber can determine whether glycine, bremelanotide, or the combination is the likely cause.

A simple approach: bring the glycine product label (dose per serving, total daily dose, timing) and your Vyleesi prescription information to the appointment or telehealth visit. Ask specifically about your personal cardiovascular and metabolic risk factors, because those, not glycine co-administration per se, are the primary safety determinants for Vyleesi users.