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PROLINA

Also known as: L-Proline, Proline, Prolina, Isoleucine-Proline-Proline (IPP), Valine-Proline-Proline (VPP)

Overview

Proline is a non-essential amino acid crucial for protein synthesis and tissue repair. It is abundant in collagen and a key component of bioactive peptides like isoleucine-proline-proline (IPP) and valine-proline-proline (VPP), often found in milk proteins. While proline itself supports protein structure and stability, its primary supplemental use lies in the blood pressure-lowering effects of IPP/VPP peptides. These peptides have been extensively studied for their ability to reduce blood pressure, particularly in individuals with hypertension. Proline's unique cyclic structure influences protein folding, and as part of IPP/VPP, it contributes to angiotensin-converting enzyme (ACE) inhibitory activity. Research on IPP/VPP peptides is robust, with numerous randomized controlled trials and meta-analyses demonstrating their efficacy, especially in Japanese populations. Proline is available in various forms, including as a free amino acid and as part of peptide-rich supplements or fermented milk products.

Benefits

The primary benefit of proline-containing peptides (IPP/VPP) is a significant reduction in systolic blood pressure (SBP). Meta-analyses of randomized controlled trials report SBP reductions ranging from 3.3 to 8.4 mm Hg, depending on baseline hypertension status. Secondary benefits include modest reductions in diastolic blood pressure (DBP), around 1.5 mm Hg. Stronger effects are observed in hypertensive individuals, with SBP reductions around 8.35 mm Hg, compared to 3.42 mm Hg in non-hypertensive subjects. The majority of evidence comes from studies on Japanese cohorts. These SBP reductions are clinically meaningful and can potentially reduce cardiovascular risk. Benefits are typically observed after several weeks of daily supplementation.

How it works

Proline-containing peptides, specifically IPP and VPP, lower blood pressure by inhibiting angiotensin-converting enzyme (ACE). This inhibition reduces the formation of angiotensin II, a potent vasoconstrictor, leading to vasodilation and a subsequent decrease in blood pressure. The primary biological pathway involves the renin-angiotensin system within the cardiovascular system. IPP and VPP peptides are absorbed intact or partially intact, with sufficient bioavailability to exert systemic ACE inhibition. The molecular target is the ACE enzyme itself, disrupting its function in converting angiotensin I to angiotensin II.

Side effects

Proline and proline-containing peptides (IPP/VPP) are generally considered safe, with no major adverse effects consistently reported in clinical trials. Common side effects are rare, with none reported above 5%. No significant adverse events have been consistently documented. However, caution is advised regarding potential additive effects with antihypertensive drugs, which could lead to excessive blood pressure lowering. Contraindications are not well-defined, but standard caution should be exercised in patients already taking blood pressure medications. Most safety data comes from studies on adults, and there is limited data available for children, pregnant women, or lactating women. Individuals with pre-existing hypotension should exercise caution.

Dosage

Effective doses of IPP/VPP peptides are typically below 5 mg/day. Meta-analyses include studies with doses both below and above this level, with significant effects observed even at lower doses. The maximum safe dose is not clearly established, but doses used in clinical trials appear to be safe. Daily intake is recommended, often as part of fermented milk products or supplements. Enzymatic or fermented forms of IPP/VPP peptides are effective. The food matrix and peptide form may influence absorption. No specific cofactors are required for proline or IPP/VPP to exert their effects.

FAQs

Is proline alone effective for blood pressure?

No, the blood pressure-lowering effects are specifically linked to proline-containing peptides (IPP/VPP), not free proline alone. These peptides have ACE-inhibiting properties.

How soon can effects be expected?

Noticeable effects on blood pressure typically appear after several weeks of consistent daily intake of IPP/VPP peptides. Individual responses may vary.

Are there risks of hypotension?

While generally safe, individuals already on antihypertensive medication should exercise caution due to the potential for additive blood pressure-lowering effects.

Can it replace antihypertensive drugs?

Proline-containing peptides may complement but should not replace prescribed medications without consulting a healthcare professional. Monitor blood pressure regularly.

Research Sources

https://pubmed.ncbi.nlm.nih.gov/26536628/ – Mizuno et al. (2015) conducted a systematic review and meta-analysis of 18 RCTs with 1194 Japanese subjects, finding that IPP/VPP peptides significantly reduced systolic blood pressure (SBP) by -5.63 mm Hg overall and -8.35 mm Hg in hypertensive individuals. The study indicated significant effects at doses below 5 mg/day, suggesting a potent effect even at low dosages. The study was limited to a Japanese population and showed heterogeneity in study designs.
https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0142235 – This is the URL for the Mizuno et al. (2015) study. The study is a systematic review and meta-analysis of 18 RCTs with 1194 Japanese subjects, finding that IPP/VPP peptides significantly reduced systolic blood pressure (SBP) by -5.63 mm Hg overall and -8.35 mm Hg in hypertensive individuals. The study indicated significant effects at doses below 5 mg/day, suggesting a potent effect even at low dosages.
https://www.mdpi.com/2223-7747/13/14/1913 – This source was not directly cited in the provided text, and therefore a summary cannot be provided. It is included as a URL only.
https://www.scirp.org/journal/paperinformation?paperid=88181 – A meta-analysis confirmed a systolic blood pressure (SBP) reduction of -3.44 mm Hg in non-hypertensive Japanese subjects and a diastolic blood pressure (DBP) reduction of -1.5 mm Hg. The study focused on non-hypertensive subjects and had limited ethnic diversity. The meta-analysis followed PRISMA guidelines, indicating a moderate to high-quality study.