A naturally-occurring peptide found in cow’s milk can reduce blood pressure by inhibiting the angiotensin-converting enzyme system. Available as a dietary supplement ingredient, this substance, known as C12-peptide, represents a novel nutritional adjunct to the management of hypertension.

Hypertension affects 50 million Americans, and another 45 million people are currently classified as pre-hypertensive (SBP 120–140, DBP 80–90 mm Hg). Epidemiologic studies show that beginning at 115/75 mm Hg, for every 20/10 mm increase, there is a doubling of mortality from both ischemic heart disease and stroke. The National Heart Lung and Blood Institute’s (www.nhlbi.nih.gov) recommendations for managing high blood pressure include lifestyle modifications and medications. These include ACE-inhibitors, diuretics, angiotensin receptor blockers, beta blockers and calcium channel blockers.

According to the guidelines, drug therapy should only be initiated after lifestyle changes have failed to reduce blood pressure to the desired level. Many anti-hypertensive medications have side effects that reduce compliance, so alternative treatments such as dietary supplements have become popular.

ACE-Inhibitory Bioactive Peptides

Lifestyle modifications including exercise and dietary changes to achieve an ideal body weight are the first approaches to achieve a healthy blood pressure. In addition, some dietary supplements may be appropriate as adjunct therapies (Engelhard YR, et al. Am Heart J. 2006; 151(1): 100; Rasmussen BM, et al. Am J Clin Nutr. 2006; 83(2): 221–226; Houston MC. Progr Cardiovasc Dis. 2005; 476(6): 396–449). Generic supplements such as vitamin E may also be used to maintain optimal antioxidant status, which supports healthy blood vessels.

Bovine milk naturally contains peptides that lower blood pressure. New technology has made it possible to enzymatically hydrolyze milk protein to produce a substance that contains high levels of the bioactive peptide responsible for this effect. This bioactive portion is called C12-peptide because it is composed of a twelve-amino-acid chain.

C12-peptide inhibits ACE, which catalyzes the conversion of angiotensin-I into angiotensin-II. Then angiotensin-II acts as potent vasopressor and synthesizes aldosterone, thereby causing renal retention of salt and water. ACE also inactivates bradykinin, inhibiting its vasodilatory action. Preliminary animal studies showed that C12-peptide can significantly reduce blood pressure by inhibiting ACE effects (Karaki H, et al. Comp Biochem Physiol. 1990; 96C: 367–371; Sugai R. Bull IDF. 1998; 336: 17–20).

Clinical Studies on C12-Peptide

The immediate effects of C12-peptide on blood pressure were evaluated in a double-blind, placebo-controlled cross-over study. Ten hypertensive subjects received either 100 mg of C12-peptide, or a similar-looking placebo on one morning. Blood pressure was measured continuously for the next 6 hours with an ambulatory blood pressure monitor (ABPM). A reduction of 8 mm Hg DBP and 6 mm Hg SBP was observed within 3–4 hours after this single dosage. Electrocardiogram (ECG), and renal, hepatic, and hematologic testing showed no evidence of toxicity or side effects (Townsend R, et al. Am J Hyper. 2004; 17: 1056–1058).

A longer-term study (four weeks) was conducted on C12-peptide in an open trial in hypertensive volunteers. Eighteen subjects received a test beverage containing 100 mg C12-peptide twice daily. Blood pressure was measured once a week in the morning. At the end of the study, diastolic and systolic blood pressures were reduced by 6.6 mm Hg and 4.6 mm Hg, respectively (Sekiya S, et al. J Jpn Soc Nutr Food Sci. 1992; 45: 513–517).

A second long-term study confirmed the previous findings. In this study, 48 pre-hypertensive subjects participated in a double-blind, placebo-controlled, parallel group design. The study had a 4-week treatment period, with either placebo or 100 mg C12-peptide tablets, taken twice daily. Blood pressure was measured once a week in the morning. After four weeks, both DBP and SBP were significantly reduced by 7 and 12 mm Hg, respectively. Significant reductions in blood pressure were evident within one week of treatment (Cadee JA, et al. 2005; in preparation). In each of these clinical trials, subjects were taken off all blood pressure-lowering drugs prior to beginning with C12-peptide, so the pressure-lowering effects were solely attributable to the supplement.

Use of milk-derived C12-peptide is an effective means of lowering blood pressure in patients with pre-hypertension or early-stage hypertension. C12-peptide supports the body’s own blood pressure control mechanism, and maximal effects can be obtained when combined with diet and exercise.

As a result of the hydrolyzation process through which it is made, C12-peptide is nearly devoid of lactose, and thus is suitable for most patients with lactose intolerance. However, it is not recommended for patients who have an allergy to the protein in cow’s milk.

Lifestyle Modifications

Lifestyle modification is the initial approach to manage blood pressure in patients with pre-hypertension or stage 1 hypertension. This includes:

• Losing weight if overweight (a 10 lbs weight loss reduces blood pressure)
• Committing to a healthy eating plan, rich in fruits, vegetables and low fat diary products and low in fat (such as the DASH eating plan)
• Reducing sodium intake (to less than 2.4 g per day)
• Reducing alcohol intake (to a maximum of two servings per day for men and one for women)
• Exercising regularly (e.g., aerobic physical activity such as brisk walking, 30 minutes per day for most days of the week)