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Last reviewed: May 12, 2026 Last updated: May 12, 2026

Written by: Jay Hastings , CEO of PlexusDx

Jay Hastings is the CEO of PlexusDx, a precision health company focused on genetic testing, blood biomarker insights, and personalized wellness recommendations. He has more than 20 years of experience across healthcare innovation, genomics, laboratory operations, healthcare investing, and strategic finance. His work has included scaling healthcare startups, leading CLIA lab integrations, and helping expand consumer access to precision health tools.

Medically reviewed by: Jayden Lee, PharmD, EMBA

Jayden Lee, PharmD, EMBA, is the PlexusDx Medical Science Liaison with a PharmD and MBA specializing in pharmacogenomics and clinical product development, with a proven ability to bridge the gap between genomic research and practical patient outcomes. Dr. Lee has more than 10 years of professional experience in clinical pharmacy, academia, and research.

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Two athletes train the same program. Same volume, same intensity, same recovery protocol. One responds by building raw power and strength that peaks in the 1–5 rep range. The other builds extraordinary endurance capacity and recovers faster between high-volume sessions. The difference isn’t solely in their muscle fibers — it’s in the vascular infrastructure that delivers oxygen, removes waste, and determines how their cardiovascular system adapts to training stress. A significant share of that difference traces to a single gene: ACE. The Precision Peptide Genetic Test analyzes the ACE I/D polymorphism as one of 15 Muscle Growth insights across 14 pathways, 49 peptides, and 150+ genetic insights.

What ACE Does

ACE encodes angiotensin-converting enzyme, a zinc-dependent metalloprotease that sits at the center of the renin-angiotensin-aldosterone system (RAAS) — the body’s primary mechanism for regulating blood pressure, fluid balance, and vascular tone. ACE performs two simultaneous actions that pull vascular physiology in the same direction:

Angiotensin conversion: ACE cleaves angiotensin I into angiotensin II, a potent vasoconstrictor that raises blood pressure, drives sodium retention, and activates multiple downstream signaling cascades including direct effects on skeletal muscle protein synthesis.

Bradykinin degradation: ACE simultaneously inactivates bradykinin, a vasodilatory peptide that promotes nitric oxide release, improves blood flow, and enhances glucose uptake in working muscle. More ACE activity means less bradykinin, which means reduced vasodilation and proportionally lower oxygen delivery efficiency to active tissue.

The net result: high ACE activity tilts cardiovascular physiology toward vasoconstriction and explosive output. Low ACE activity tilts it toward vasodilation, oxygen efficiency, and endurance capacity. Your ACE genotype determines where on that spectrum your vascular system sits at baseline.

The I/D Polymorphism: The Most Replicated Sport Gene Variant

The ACE gene contains a 287-base-pair insertion/deletion (I/D) polymorphism in intron 16 — a non-coding region whose presence (I allele) or absence (D allele) dramatically affects how much ACE enzyme the body produces:

II genotype: Two insertion alleles. Lowest ACE enzyme activity. Best vasodilation efficiency, highest bradykinin levels, superior oxygen delivery per unit of cardiac output. Strongly overrepresented among elite endurance athletes — distance runners, cyclists, rowers, triathletes. Associated with higher VO₂max capacity and better economy of effort at submaximal intensities.

ID genotype: One of each. Intermediate ACE activity. The most common genotype in most populations — roughly 50% of people carry this combination. Physiologically versatile: capable of meaningful endurance and power adaptation, making training specialization more impactful than genotype alone.

DD genotype: Two deletion alleles. Highest ACE enzyme activity. Greatest angiotensin II production, most active vasoconstriction response to exercise, lowest bradykinin levels. Overrepresented among elite sprinters, power lifters, and strength athletes. Associated with greater acute strength gains, more pronounced muscle hypertrophy response to resistance training, and higher peak anaerobic power output.

The ACE I/D finding is among the best-replicated results in sport genetics — documented across dozens of independent populations, multiple athletic disciplines, and several ethnic groups. The direction of the effect is consistent even when the magnitude varies: I allele for endurance, D allele for power.

What Your ACE Genotype Means for Training Response

ACE genotype doesn’t determine athletic destiny — it reveals the cardiovascular architecture your training response is built on. Knowing that architecture lets you design training that amplifies your natural advantages rather than fighting against them.

II genotype athletes recover faster between high-volume sessions because bradykinin-driven vasodilation accelerates lactate clearance and oxygen resaturation in muscle. They tend to respond better to polarized training models (heavy volume at low intensity + occasional high-intensity efforts) and may see diminishing returns from pure strength periodization relative to ID or DD counterparts.

DD genotype athletes generate stronger acute hypertrophic and strength responses to resistance training, partly through the direct protein-synthesis signaling of elevated angiotensin II (discussed below). They tend to respond well to higher-intensity, lower-volume strength blocks and may plateau faster in pure endurance volume without complementary intensity variation.

ID genotype athletes have the most physiological flexibility — their intermediate ACE activity allows meaningful adaptation in both directions, making them highly responsive to training specialization. Sport selection and training focus carry more weight for ID individuals than genotype alone.

ACE, Angiotensin II, and Direct Muscle Anabolism

The connection between ACE and muscle growth isn’t purely cardiovascular. Angiotensin II — the product of ACE enzyme activity — has documented direct anabolic effects on skeletal muscle through its AT1 receptor (AT1R). When angiotensin II binds AT1R on muscle cells, it activates ERK1/2 and mTOR-independent protein synthesis pathways that promote hypertrophy separately from the GH→IGF-1 axis.

This means DD genotype individuals operate with a secondary anabolic signal that II genotype individuals lack. The trade-off is vascular: that same elevated angiotensin II that supports hypertrophy also raises baseline vascular resistance, which costs endurance efficiency. Neither outcome is better or worse — they are different physiological configurations suited to different performance demands.

ACE and Growth Hormone Axis Pathways

ACE genotype shapes the vascular infrastructure through which growth hormone axis anabolic signals physically reach muscle tissue. GH stimulates IGF-1 production in the liver; IGF-1 travels through the bloodstream to muscle; muscle satellite cells and fiber surfaces receive and respond to that signal. The efficiency of that delivery depends in part on the vasodilation capacity of the capillary beds supplying working muscle — which ACE genotype governs.

For individuals with II genotype, superior bradykinin-driven vasodilation may enhance IGF-1 delivery to working muscle beds during and after training. For DD genotype individuals, the direct anabolic action of angiotensin II via AT1R adds a parallel, GH-axis-independent protein synthesis signal that compounds with IGF-1 signaling. Reading ACE genotype alongside IGF1, GHSR, and GHR gives a more complete picture of how anabolic signals are generated, delivered, and received across your full growth hormone axis architecture.

The Full Muscle Growth Genetic Panel

ACE is the cardiovascular architecture gene in the Precision Peptide Genetic Test’s 15 Muscle Growth insights — the gene that determines the vascular infrastructure through which every other anabolic signal operates:

ACTN3 (R577X) — fast-twitch fiber composition; ACE DD genotype compounds with ACTN3 RR genotype to produce the most pronounced power-athlete profile in the panel.

MSTN (myostatin) — hypertrophy ceiling; the direct anabolic signaling of angiotensin II in DD carriers operates upstream of myostatin suppression, so MSTN genotype shapes how much of that signal converts to mass.

IGF1 — growth hormone axis downstream mediator; ACE genotype influences the vascular delivery efficiency of circulating IGF-1 to target muscle.

GHSR — ghrelin receptor and GH release trigger; the GH pulses GHSR initiates drive the IGF-1 that ACE-determined vasculature delivers.

GHR — growth hormone receptor; determines how sensitively the liver responds to GH to generate the IGF-1 that muscle vasculature must deliver.

VDR — vitamin D receptor; VDR-mediated upregulation of IGF-1 receptor density compounds with ACE-determined delivery efficiency.

IL-6 — the post-exercise inflammation gene; ACE genotype influences vascular inflammatory response during recovery, creating interactions with the IL-6-driven repair cascade.

Cross-pathway, ACE findings extend into 12 Energy Metabolism insights (cardiovascular efficiency is a core energy metabolism variable) and 9 Tissue Repair insights (tissue perfusion drives repair speed). ACE is a systemic gene whose effects compound throughout the panel.

The Precision Peptide Genetic Test analyzes how your genes influence muscle growth pathways. It does not recommend, prescribe, or determine which peptides you should use. Consult a qualified healthcare provider before beginning any peptide protocol.

Ready to see which side of the endurance-power spectrum your genetics favor? Take the Precision Peptide Genetic Test

Frequently Asked Questions About ACE Gene and Athletic Performance

What does the ACE I/D variant reveal about athletic performance?

The ACE I/D polymorphism determines cardiovascular and metabolic optimization — I allele carriers have lower ACE activity, better vasodilation, and superior endurance capacity; D allele carriers have higher ACE activity and greater power and strength adaptation. The Precision Peptide Genetic Test analyzes ACE as part of 15 Muscle Growth insights and 150+ total genetic insights.

Does ACE genotype affect how growth hormone axis pathways respond?

ACE genotype shapes tissue perfusion and cardiovascular response to training — the infrastructure through which GH axis signals reach muscle. D allele carriers may experience more pronounced protein synthesis responses due to angiotensin II signaling. Knowing your ACE result helps frame how growth hormone axis pathway protocols may interact with your cardiovascular physiology.

What other genes are analyzed alongside ACE in the muscle growth panel?

The Precision Peptide Genetic Test analyzes 15 Muscle Growth insights — including ACTN3 (fiber type), MSTN (myostatin ceiling), IGF1 (growth hormone axis signaling), GHSR (ghrelin receptor), GHR (growth hormone receptor), VDR (vitamin D and muscle), and IL-6 (inflammation and recovery). ACE is the cardiovascular architecture gene in a multi-gene muscle profile.

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Medical and Editorial Standards

Medical review process: This article was reviewed for medical accuracy, scientific clarity, evidence alignment, and appropriate discussion of genetics, medications, supplements, biomarkers, and health-related claims.

Sources and evidence: PlexusDx educational content is developed using peer-reviewed research, clinical literature, reputable medical references, and, where applicable, public health or regulatory guidance. References are included at the end of the article when scientific, medical, or health-related claims are discussed.

Commercial transparency: PlexusDx offers genetic testing, blood biomarker testing, personalized supplement recommendations, and related precision wellness services. Product mentions are intended to help readers understand available options and should not be interpreted as medical advice.

Important disclaimer: PlexusDx educational content is for informational purposes only and should not be used as a substitute for professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before making decisions about medications, supplements, genetic testing, lab testing, or health-related care.