The first significant effects of lactotripeptides on BP in hypertensive subjects have been observed after 1–2 weeks of treatment with dosages as low as 3.8 mg/day. † First part of the study was carried out in parallel design and second part of the study was carried out in crossover design. ∗ Results reported as changes in SBP and DBP after each month of treatment for all subjects (intention-to-treat analysis), and as mean changes over the total intervention period among subjects who had BP measurements for each month (per protocol analysis). IPP, Isoleucine-proline-proline VPP, valine-proline-proline SBP, systolic blood pressure DBP, diastolic blood pressure R, p-c, d-bld, randomized, placebo-controlled, double-blinded. Lactobacillus, Saccharomyces helveticus & Saccharomyces cerevisiaeĦ4 Asian subjects with SBP 140–159 and DBP 90–99 mmHgģ2 Asian subjects with SBP 140–180 and DBP 90–105 mmHgġ8 Asian hypertensive and 26 normotensive subjectsģ0 Asian subjects with SBP 140–180 and DBP 90–105 mmHgġ44 Asian subjects with high-normal or mild hypertensionģ9 Finnish subjects with SBP 133–176 and DBP 86–108 mmHgĦ0 Finnish subjects with SBP 140–180 and DBP 90–110 mmHgĢ0 Asian healthy volunteers with normal blood pressure (<130 mmHg SBP and <85 mmHg DPB)Ģ75 Dutch subjects with mild hypertensionġ35 Dutch subjects with untreated high-normal BP or mild hypertensionħ0 Caucasian subjects with pre-hypertension or stage 1 hypertension Thereafter, a further gradual lowering is seen, but to a lesser extent than in the first period ( Kajimoto, Aihara, et al., 2001 Seppo et al., 2003). From these data, it becomes apparent that the largest part of the total BP reduction takes place in the first 1–2 weeks of treatment. Generally, maximum duration of treatment has been 8 weeks at doses between 3 and 52 mg/day ( Table 3.3). The human studies with lactotripeptides have been done mainly in Japanese subjects and some in Finnish subjects ( Aihara, Kajimoto, Hirata, Takahashi, & Nakamura, 2005 Hata et al.,1996 Jauhiainen, Vapaatalo, et al., 2005 Kajimoto, Aihara, Hirata, Takahashi, & Nakamura, 2001 Kajimoto, Nakamura, et al., 2001 Nakamura et al., 2004 Seppo, Jauhiainen, Poussa, & Korpela, 2003 Seppo, Kerojoki, Suomalainen, & Korpela, 2002). Most clinical trials have assessed blood pressure (BP)-lowering effects at multiple points over time. Oral administration of these tripeptides included different formulas, such as fermented milk, tablets, capsules, fruit juice and other products. More than 20 human studies have been published linking the consumption of products containing lactotripeptides with significant reductions in both SBP and diastolic blood pressure (DBP). So far, most of the clinical research has focused on lactotripeptides and their anti-hypertensive properties. Evidence of the beneficial effects of bioactive peptides has to be based on studies performed in humans.
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