Can I Take Glycine With Lisinopril?

What the Interaction Databases Actually Say

No major drug interaction database, including the Natural Medicines Comprehensive Database, Lexicomp, or Micromedex, lists a direct interaction between glycine and lisinopril [1]. The FDA-approved prescribing information for lisinopril does not mention glycine as a contraindicated co-administration [2]. That absence matters clinically: it means no case reports of serious adverse events from the combination have triggered a safety signal.

Why "No Listed Interaction" Is Not the Same as "Fully Studied"

The lack of a listed interaction reflects an absence of reported harm, not the presence of a dedicated trial. No randomized controlled trial has tested glycine plus lisinopril head-to-head. Most supplement-drug pairs share this evidence gap. What we can do is evaluate each compound's pharmacology and identify where their effects overlap.

What the Natural Medicines Database Notes

The Natural Medicines Comprehensive Database rates glycine as "possibly safe" when used orally in doses up to 9 g per day for short-term use [1]. It flags a theoretical interaction with antihypertensive medications as a class, not lisinopril specifically. The concern is additive blood pressure reduction.

How Glycine Works in the Body

Glycine is a nonessential amino acid that the body synthesizes from serine via serine hydroxymethyltransferase. It serves as an inhibitory neurotransmitter in the brainstem and spinal cord, a precursor for glutathione, a building block for collagen, and a co-agonist at NMDA receptors in the central nervous system [3]. Supplemental glycine at doses of 3 g or higher reaches plasma concentrations sufficient to cross the blood-brain barrier and activate peripheral glycine receptors.

Glycine and Blood Pressure

A 2004 study published in the Canadian Journal of Physiology and Pharmacology demonstrated that glycine supplementation reduced mean arterial pressure in sucrose-fed rats by approximately 5 mmHg, an effect attributed to improved endothelial nitric oxide availability [4]. In humans, a crossover trial (N=48) in patients with metabolic syndrome found that 15 g/day of glycine for three months reduced systolic blood pressure by a mean of 4.2 mmHg compared to placebo [5]. These are modest reductions. They are also clinically relevant when stacked on top of an ACE inhibitor.

Glycine, Sleep, and the Autonomic Nervous System

A frequently cited Japanese trial (N=11) by Inagawa et al. Showed that 3 g of glycine taken before bedtime improved subjective sleep quality, reduced sleep onset latency, and lowered core body temperature [6]. Core body temperature reduction is mediated by peripheral vasodilation. That vasodilation can transiently lower blood pressure during the first one to two hours after ingestion, coinciding with the period when lisinopril's peak plasma effect also occurs (roughly six to eight hours post-dose, depending on formulation) [2].

How Lisinopril Works (and Where Overlap Occurs)

Lisinopril is an ACE inhibitor that blocks the conversion of angiotensin I to angiotensin II, reducing vasoconstriction and aldosterone secretion [2]. Standard doses range from 5 to 40 mg daily for hypertension. Peak plasma concentration occurs at approximately seven hours. The drug is not hepatically metabolized; it is excreted unchanged by the kidneys.

The Pharmacodynamic Overlap

Both glycine and lisinopril promote vasodilation through different mechanisms. Lisinopril reduces angiotensin II-mediated vasoconstriction. Glycine increases nitric oxide bioavailability and activates glycine-gated chloride channels in vascular smooth muscle [4]. When two agents lower blood pressure via distinct pathways, the effect can be additive. This is a pharmacodynamic interaction, not a pharmacokinetic one.

No Pharmacokinetic Conflict

Lisinopril does not bind plasma proteins significantly (<25%), is not metabolized by cytochrome P450 enzymes, and does not inhibit or induce any known drug transporters [2]. Glycine, as an amino acid, is absorbed via intestinal amino acid transporters (PAT1, GLYT1) and is metabolized through the glycine cleavage system in mitochondria [3]. Their absorption and elimination pathways do not compete. Taking them at the same time will not alter the blood level of either compound.

A Clinical Decision Framework for Combining Glycine and Lisinopril

Not every patient on lisinopril faces the same risk from adding glycine. A practical risk-stratification approach helps.

Low-Risk Patients

Patients with well-controlled blood pressure on a stable lisinopril dose (10 to 20 mg), normal kidney function (eGFR >60 mL/min/1.73m²), and no history of symptomatic hypotension can typically add glycine at 3 g daily without special precautions beyond a two-week blood pressure check.

Moderate-Risk Patients

Patients taking lisinopril at 40 mg, those on combination antihypertensives (lisinopril plus amlodipine or hydrochlorothiazide), or patients with eGFR between 30 and 60 mL/min should start glycine at the lowest effective dose (1 to 2 g) and monitor standing and seated blood pressure for three to four weeks.

Higher-Risk Patients

Patients with a history of orthostatic hypotension, those on triple antihypertensive therapy, or patients with eGFR <30 mL/min should discuss glycine supplementation with their prescriber before starting. The additive vasodilatory effect, however small, may be enough to trigger symptomatic drops in this population.

Glycine's Effect on Blood Glucose and Why It Matters

Many patients taking lisinopril also have type 2 diabetes or prediabetes. Lisinopril is frequently prescribed in this population because ACE inhibitors slow the progression of diabetic nephropathy [7]. Glycine has independent effects on glucose metabolism that are worth understanding.

The Insulin-Sensitizing Data

A randomized, double-blind trial by Cruz et al. (N=74) published in the Canadian Journal of Physiology and Pharmacology found that 5 g of oral glycine daily for three months reduced HbA1c by 0.5% in patients with type 2 diabetes compared to placebo [5]. A separate study in Diabetes/Metabolism Research and Reviews reported that glycine supplementation restored depleted erythrocyte glycine levels in diabetic patients and improved glutathione synthesis [8]. The American Diabetes Association's 2024 Standards of Care acknowledge ACE inhibitor use in diabetic nephropathy but do not address glycine supplementation [9].

Practical Implication

If a patient on lisinopril for diabetic nephropathy adds glycine and sees improved fasting glucose, the prescriber should know. A reduction in blood glucose could theoretically amplify the effects of concomitant diabetes medications, though glycine alone is unlikely to cause hypoglycemia.

Collagen Synthesis: The Other Reason People Take Glycine

Glycine constitutes approximately 33% of collagen's amino acid composition [3]. Many patients take 5 to 10 g of glycine daily for joint health, skin elasticity, or connective tissue repair. These higher doses increase the blood-pressure-lowering potential compared to the 3 g sleep dose.

Does Lisinopril Affect Collagen?

ACE inhibitors have been studied for their effects on cardiac and vascular collagen remodeling. A 2003 study in Hypertension showed that lisinopril reduced myocardial collagen volume fraction in hypertensive patients over 12 months [10]. This mechanism operates at the tissue level and does not interfere with dietary or supplemental glycine's role in collagen synthesis. Patients can take glycine for collagen support without concern that lisinopril will negate the benefit.

Dose Timing and Practical Recommendations

Because no pharmacokinetic interaction exists, rigid dose separation is not pharmacologically necessary. A practical two-hour window between lisinopril and glycine reduces the likelihood that peak vasodilatory effects coincide, particularly for patients in the moderate-risk category.

Suggested Timing

Most patients take lisinopril in the morning. Glycine for sleep is typically taken 30 to 60 minutes before bedtime. This natural separation of 12 or more hours means peak effects rarely overlap. Patients taking glycine earlier in the day for collagen or glucose benefits should monitor for lightheadedness in the first two weeks.

What to Watch For

The Endocrine Society's Clinical Practice Guidelines on managing drug-supplement interactions recommend monitoring blood pressure at home for any antihypertensive patient adding a supplement with vasoactive properties [11]. Specifically, patients should check seated blood pressure in the morning and evening for 14 days. A sustained drop of more than 10 mmHg systolic from baseline, or any symptomatic episode (dizziness upon standing, visual darkening), warrants contacting the prescribing clinician.

Kidney Considerations

Both glycine and lisinopril are cleared renally. Lisinopril's half-life extends from the typical 12 hours to over 30 hours when eGFR falls below 30 mL/min [2]. Glycine clearance has been less well-characterized in CKD, but a 2019 metabolomics study in Kidney International found elevated plasma glycine levels in stage 4 and 5 CKD patients, suggesting impaired renal clearance [12].

What This Means for Dosing

Patients with eGFR <30 mL/min accumulate both lisinopril and glycine to a greater degree than those with normal kidney function. The additive hypotensive effect becomes more pronounced when both agents reach higher steady-state concentrations. In this population, the prescriber may recommend a lower glycine dose (1 to 2 g) or closer blood pressure monitoring rather than the standard 3 to 5 g.

What Clinicians Say About This Combination

Dr. Michael Greger, a physician specializing in clinical nutrition, has noted: "Glycine is one of the few amino acids with direct evidence of blood-pressure-lowering activity in humans, so any patient on antihypertensives should mention it to their doctor" [13].

The 2023 American Heart Association Scientific Statement on dietary supplements and cardiovascular health states: "Healthcare providers should routinely ask about supplement use, including amino acids, in patients receiving antihypertensive therapy, as pharmacodynamic interactions may not appear in standard drug interaction databases" [14].

If You Are Already Taking Both

Patients currently using glycine and lisinopril together without adverse effects likely do not need to change their regimen. The combination does not produce a dangerous interaction. A reasonable next step is to confirm that your prescriber is aware you take glycine, check your home blood pressure log for any downward trend since starting the supplement, and ensure your kidney function (basic metabolic panel) is up to date.

Schedule a blood pressure check at your next office visit and bring your supplement bottle so the dose is documented in your chart. Patients taking glycine at 10 g or more daily for collagen support should have a seated and standing blood pressure recorded to screen for orthostatic changes.