Can I Take Glycine with Losartan?

How Losartan Works and Why Interactions Matter

Losartan is an angiotensin II receptor blocker (ARB) approved for hypertension, heart failure with reduced ejection fraction, and diabetic nephropathy in patients with type 2 diabetes. It blocks the AT1 receptor, reducing vasoconstriction, aldosterone release, and sodium retention [1]. The liver converts losartan to its active metabolite EXP-3174 through CYP2C9 (primary) and CYP3A4 (minor) [2].

Why Supplement Interactions Get Overlooked

Any substance that lowers blood pressure, alters hepatic enzyme activity, or shifts renal electrolyte handling could theoretically interact with an ARB. Glycine is a non-essential amino acid sold as a sleep aid, a collagen precursor, and a metabolic supplement. Because it is classified as a dietary supplement, the FDA does not require interaction studies before it reaches store shelves.

The Practical Question

Patients taking losartan 25 to 100 mg daily often ask about adding glycine 3 g at bedtime for sleep quality. The question is whether that combination introduces clinically meaningful risk. The short answer: for most people, it does not.

Is There a Pharmacokinetic Interaction Between Glycine and Losartan?

No pharmacokinetic interaction between glycine and losartan has been identified in published literature, the Natural Medicines Comprehensive Database, or the FDA adverse event reporting system. This is expected based on their distinct metabolic pathways.

CYP Enzyme Considerations

Losartan depends on CYP2C9 for conversion to EXP-3174. Drugs that inhibit CYP2C9 (fluconazole, amiodarone) can raise losartan levels and reduce active metabolite formation [2]. Glycine is a simple two-carbon amino acid that enters intermediary metabolism through the glycine cleavage system in mitochondria. It does not interact with cytochrome P450 enzymes at supplemental doses of 1 to 9 g daily [3].

Absorption and Bioavailability

Glycine is absorbed in the small intestine via active amino acid transporters. Losartan is also absorbed in the proximal small intestine, with approximately 33% oral bioavailability [2]. There is no evidence that glycine competes with losartan for absorption or alters its bioavailability. Taking them at the same time is unlikely to change plasma concentrations of either substance.

What About the Active Metabolite?

EXP-3174 is 10 to 40 times more potent than losartan at the AT1 receptor and accounts for most of the drug's antihypertensive effect [2]. Because glycine does not affect CYP2C9, the ratio of losartan to EXP-3174 should remain unchanged when glycine is added.

The Pharmacodynamic Overlap: Blood Pressure

The interaction worth paying attention to is pharmacodynamic, not pharmacokinetic. Both substances may lower blood pressure through independent mechanisms.

Glycine and Vascular Tone

A 2004 study in rats showed that intravenous glycine reduced mean arterial pressure by increasing nitric oxide (NO) availability through glycine-gated chloride channels on endothelial cells [4]. A small crossover trial in humans (N=48) found that 5 g of oral glycine daily for three months reduced systolic blood pressure by approximately 4 mmHg compared to placebo, though the result did not reach statistical significance (P=0.07) [5].

Additive Hypotension Risk

Losartan 50 to 100 mg typically reduces systolic blood pressure by 8 to 12 mmHg [1]. If glycine adds another 2 to 4 mmHg of reduction, the combined effect could push susceptible patients into symptomatic hypotension. This is most relevant for:

• Adults over 65 with baseline systolic BP below 110 mmHg
• Patients on multiple antihypertensives (losartan plus amlodipine plus hydrochlorothiazide, for example)
• People who are volume-depleted from diuretics, illness, or inadequate fluid intake

For a patient whose resting BP is 135/85 on losartan 50 mg, adding glycine 3 g at bedtime poses minimal hypotension risk.

Practical Blood Pressure Monitoring

Take home BP readings twice daily (morning before medication, evening before glycine) for the first 14 days after starting the combination. If systolic BP drops below 100 mmHg or you experience dizziness upon standing, reduce glycine to 1 g and reassess.

Glycine, Glucose, and Diabetic Nephropathy

Many losartan prescriptions target diabetic nephropathy. The RENAAL trial (N=1,513) demonstrated that losartan 50 to 100 mg reduced the risk of doubling serum creatinine by 25% and end-stage renal disease by 28% in patients with type 2 diabetes [6]. Glycine has its own metabolic profile that intersects with this patient population.

Glycine and Insulin Sensitivity

A randomized trial by Cruz et al. (N=74 patients with metabolic syndrome) found that 15 g of glycine daily for three months reduced HbA1c by 0.5% and HOMA-IR by 1.3 units compared to placebo (P<0.01 for both) [7]. A separate trial (N=60, type 2 diabetes) showed that 5 g of glycine before each meal reduced postprandial glucose by approximately 15 mg/dL at 60 minutes [8].

Is This Beneficial or Risky?

For patients with diabetic nephropathy on losartan, a modest improvement in glycemic control could be beneficial. The risk is hypoglycemia in patients also taking sulfonylureas or insulin. A fasting glucose drop from 140 to 125 mg/dL is helpful. A drop from 90 to 75 mg/dL in someone on glipizide is not.

Decision Framework: Glycine in the Diabetic Nephropathy Patient on Losartan

1. Fasting glucose consistently above 130 mg/dL on stable diabetes regimen: glycine 3 to 5 g daily is reasonable; monitor fasting glucose weekly for four weeks.
2. Fasting glucose 100 to 130 mg/dL on sulfonylurea or insulin: start glycine at 1 g daily, titrate slowly, and check glucose before breakfast and before bed.
3. Fasting glucose below 100 mg/dL on any hypoglycemic agent: discuss with prescriber before adding glycine.

Glycine for Sleep: Timing Relative to Losartan

The most common reason patients combine these two is sleep. A double-blind crossover study (N=11) published in Sleep and Biological Rhythms found that 3 g of glycine taken before bed reduced sleep onset latency and improved subjective sleep quality without morning sedation [9]. A larger trial (N=19) by Bannai et al. Replicated these findings using polysomnography and next-day cognitive testing [10].

When to Take Each

Losartan is typically dosed once daily in the morning, though some clinicians prescribe it at bedtime for patients with non-dipping nocturnal hypertension. Glycine for sleep is taken 30 to 60 minutes before bed.

Morning Losartan, Bedtime Glycine

This is the simplest approach. The doses are separated by 12 or more hours, and any additive BP-lowering effect from glycine coincides with the natural nocturnal dip rather than the peak plasma concentration of losartan (which occurs one to two hours after an oral dose) [2].

Bedtime Losartan and Bedtime Glycine

If your clinician has prescribed losartan at night, taking glycine at the same time is still acceptable. The two are not competing for the same enzymes or transporters. The concern is only whether the combined BP reduction at 2 a.m. Causes orthostatic symptoms when you get up to use the bathroom. For patients over 65, a two-hour separation (losartan at 8 p.m., glycine at 10 p.m.) adds a margin of safety.

Collagen Synthesis: Does It Affect Losartan Efficacy?

Glycine constitutes roughly one-third of the amino acid residues in collagen. Patients taking glycine for joint health, skin elasticity, or tendon recovery sometimes wonder whether increased collagen turnover could affect the cardiovascular system or losartan's mechanism.

Vascular Collagen Remodeling

ARBs reduce angiotensin II-mediated collagen deposition in the heart and arterial walls, which is part of their cardioprotective effect [11]. Supplemental glycine at 3 to 9 g daily does not override this pharmacologic effect. Collagen synthesis requires not just glycine but also proline, hydroxyproline, vitamin C, and appropriate signaling from growth factors. Oral glycine supplementation supports connective tissue repair in musculoskeletal contexts without reversing the anti-fibrotic action of an ARB.

The Bottom Line on Collagen

Glycine for collagen support does not interfere with losartan's cardiovascular or renal protective effects at standard supplemental doses.

Renal Considerations

Losartan reduces intraglomerular pressure by blocking angiotensin II at the efferent arteriole. This is protective in diabetic nephropathy but also means any additional drop in renal perfusion pressure could theoretically reduce GFR.

Glycine and Kidney Function

Glycine has been studied as a renoprotective agent in ischemia-reperfusion models. A 2008 study showed that glycine administration reduced tubular necrosis and inflammatory cytokine release in rat kidneys subjected to warm ischemia [12]. In humans with CKD stages 1 to 3, glycine supplementation at 3 to 5 g daily has not been associated with worsening creatinine or cystatin C levels in the available (limited) data.

Who Needs Extra Caution

Patients with eGFR below 30 mL/min/1.73m² should discuss glycine supplementation with their nephrologist. Amino acid metabolism shifts in advanced CKD, and glycine clearance may be reduced. This is a general precaution for all amino acid supplements in advanced kidney disease, not specific to a losartan interaction.

What If You Are Already Taking Both?

If you have been combining glycine and losartan without symptoms, there is likely no reason to stop. Check these three items:

1. Home blood pressure: measure morning and evening for one week. If all readings are above 95/60, the combination is hemodynamically tolerable.
2. Fasting glucose (if diabetic): confirm no unexpected drops below your target range.
3. Symptom check: no new dizziness, lightheadedness on standing, or unusual fatigue.

If all three are clear, continue. Report any new symptoms to your prescribing clinician.

When to Involve Your Prescriber

A brief call or patient portal message to your prescriber is appropriate if:

• You are on three or more antihypertensives and want to add glycine
• Your last eGFR was below 45 mL/min/1.73m²
• You take insulin or a sulfonylurea for diabetes
• You have experienced orthostatic hypotension in the past six months
• You plan to exceed 5 g of glycine daily

The Endocrine Society and the American Heart Association do not have specific guidelines addressing the glycine-losartan combination, so prescriber judgment based on your individual hemodynamic and metabolic profile is the appropriate standard [13][14].