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ACE Reasons for Consuming Sheep’s Milk

    Sheep herd grazing on wheat stubble; sheep's milk may be used to treat high blood pressure

    Written by: Anna Petherick, Ph.D. | Issue # 75 | 2018

    • Sheep’s milk is widely used in cheese making, which results in large amounts of the waste product, sheep’s milk whey.
    • Researchers have shown that commercially available bacterial proteases successfully release bioactive peptides from sheep’s milk whey, and that these peptides control blood pressure.
    • These bioactive peptides may lower blood pressure by inhibiting ACE (angiotensin-converting enzyme).
    • Human digestion probably releases more of these blood pressure-controlling peptides from sheep’s milk than from cow’s, goat’s, or camel’s milks.

    Sheep milk is not a regular feature on supermarket shelves, except in the form of cheese. In fact, many well-known cheeses—Feta, Manchego, and Roquefort among them—are made of sheep’s milk, often unbeknownst to consumers. It is the particular composition of sheep’s milk that makes it so good for cheese making. In short, sheep’s milk is very high in solids, containing quite a bit of fat and almost double the protein content of goat’s milk and cow’s milk [1]. But the process of making cheese leaves a lot of waste. And, according to recent studies, this leftover liquid (or whey) could find a use in the creation of novel products containing bioactive peptides. The bioactive peptides from sheep’s milk whey are of interest because they are unusually good at lowering blood pressure.

    One group of researchers who have investigated the possibility of re-purposing sheep’s milk whey is based at the University of Otago in Dunedin, New Zealand. They wanted to know which of two kinds of commercially available, food-grade protease preparations (combinations of protein-digesting enzymes) would do a better job at breaking down the proteins in sheep’s milk whey and releasing bioactive peptides [2]. Their preparations were composed of either bacterial or fungal enzymes.

    What it meant to “do a better job” in their 2017 study had several considerations. It meant to generate a soup of broken-down proteins with high antioxidant activity, strong ability to inhibit ACE (angiotensin-converting enzyme), to not show any signs of toxicity towards mammalian cells, and to remain stable through various chemical and physical treatments intended to simulate human digestion. The experiments showed that the bacterial protease preparation is the way to go; it was preferable to the fungal preparation by all four measures.

    But what is ACE, and why would peptides able to inhibit it be of value? Among other roles in the body, this enzyme is involved in the regulation of blood pressure. It does this by converting a hormone called angiotensin I into the blood vessel-constricting angiotensin II [3]. Of course, when blood vessels constrict, the same amount of blood finds itself in a smaller overall space, so blood pressure rises. Because ACE inhibitors reduce the conversion of angiotensin I to angiotensin II, they keep blood pressure down. Unsurprisingly, for several decades now, there has been a huge market for medicines that have this effect.

    Various studies have shown that sheep’s milk is a rich source of ACE-inhibitors [1]. But, as was well known to the researchers in Dunedin, the proteins in milk need to be broken down for the activity to be fully apparent. This makes the ACE-inhibitor activity of the milks of different mammals difficult to compare. It’s neither easy nor comfortable to extract partially digested material from a living human, and so the activity of the peptides that result from the real-life digestion of different mammal’s milks is not known.

    In January 2018, however, a team led by Davide Tagliazucchi of the University of Modena and Reggio Emilia, in Modena, Italy, did the next best thing [4]. The researchers used a laboratory protocol to imitate the salivary, gastric, and intestinal stages of digestion, on one type of milk at a time. This way they could compare the peptides released from cow’s, camel’s, goat’s and sheep’s milks. After each stage of digestion, samples were taken. The team recorded how well the partially digested milky mixtures were able to quench free radicals, and for the peptide fractions of the post-pancreatic-digestion samples, they measured the ability to inhibit ACE.

    Using mass spectrometry, this team showed that goat’s milk and sheep’s milk had the greatest diversity of peptides. The free-radical scavenging test found that undigested sheep’s milk performed better than the other milks, and that after digestion, it was equally as effective as goat’s milk. (Both of these were better free-radical scavengers than digested cow’s milk and digested camel’s milk.) But it was the ACE-inhibition test where sheep’s milk really stood out. For this test, activity was measured in units called “IC50,” indicating the concentration of peptide that was required to cut ACE activity by one half. Sheep’s milk was by far the most potent ACE inhibitor—about 626 micrograms of peptides per milliliter did the job of reducing ACE activity 50%; cow’s milk, meanwhile, required almost 2,400 micrograms of peptide per milliliter.

    So, if digested sheep’s milk and digested sheep’s milk whey are such a good sources of blood pressure control, what kind of products might its bioactive peptides find their way into? All kinds of health foods are possibilities. In late February 2018, Senaka Ranadheera of the University of Melbourne, and his colleagues, proposed making ice cream out of sheep’s milk [5]. Their suggestion is motivated by the fact that probiotics such as Lactobacillus casei are thought to be well protected on their journey from mouth to intestines in ice cream made of sheep’s milk, but there is little reason why bioactive peptides could not be sprinkled in.

    Imagine. Ice cream that lowers blood pressure.


    1. C.F. Balthazar, T.C. Pimentel, L.L. Ferrão, C.N. Almada, A. Santillo, M. Albenzio, N. Mollakhalili, A.M. Mortazavian, J.S. Nascimento, M.C. Silva, M.Q. Freitas, A.S. Sant’Ana, D. Granato & A.G. Cruz. 2017. Sheep milk: Physicochemical characteristics and relevance for functional food development. Comprehensive Reviews in Food Science and Food Safety. 16(2), 247–262.
    2. G. Welsh, K.Ryder, J. Brewster, C.Walker, S. Mros, A. E-D. A. Bekhit, M. McConnell & A. Carne. 2017. Comparison of bioactive peptides prepared from sheep cheese whey using a food-grade bacterial and a fungal protease preparation. International Journal of Food Science and Technology. 52, 1252–1259.
    3. K. R. Acharya, E. D. Sturrock, J. F. Riordan & M. R. W. Ehlers. 2003. Ace revisited: A new target for structure-based drug design. Nature Reviews Drug Discovery. 2, 891–902.
    4. D. Tagliazucchi, S. Martini, S. Shamsia, A. Helal & A. Conte. 2018. Biological activities and peptidomic profile of in vitro-digested cow, camel, goat and sheep milk. International Dairy Journal. doi: 10.1016/j.idairyj.2018.01.014.
    5. C.S. Ranadheera, N. Naumovski & S. Ajlouni. 2018. Non-bovine milk products as emerging probiotic carriers: recent developments and innovations. Current Opinions in Food Science. doi:10.1016/j.cofs.2018.02.010