Puleva looks to goat's milk proteins to prevent hypertension
ingredient to prevent the development of high blood pressure, if
results from a rat study can be translated to humans.
Lead researcher Arjen Geerlings from Puleva Biotech told NutraIngredients.com that they are now taking the caseins to the human clinical trial stage, with a three-month intervention trial with about 40 borderline-hypertensives planned to participate.
Puleva see the potential market as just as big as the cholesterol-lowering market. "There are a lot of hypertensive people out there," said Geerlings. "And most people don't know it."
Indeed, in the UK alone, there are an estimated 10m people with hypertension, defined as having blood pressure higher than 140/90 mmHg. The condition is a major risk factor for cardiovascular disease (CVD), which causes almost 50 per cent of deaths in Europe, and is reported to cost the EU economy an estimated €169bn ($202bn) per year.
The new study, published in the Journal of Dairy Science, looked at the effect of three hydrolysed caseins from fat-free goat's milk, purchased from a local supplier.
The hydrolysis was achieved using subtilisin alcalase enzymes, provided by Novozymes.
"An alignment of the amino acid sequences of the four main proteins found in bovine and goat milk identified differences between these two species," wrote the researchers. "Therefore, we use this less-explored source of protein for the identification of novel ACE inhibitors."
The three hydrolysed caseins, listed as beta-CN f78-83, beta-CN f84-87, beta-CN f181-184, were added to the diets of 10 spontaneaous hypertensive rats (SHR). A further 10 SH rats were supplemented with normal goat protein (control), and another 10 rats were fed diet containing normal goat protein and captopril, a pharmaceutical ACE-inhibitor.
ACE inhibitors work by inhibiting the conversion of angiotensin I to the potent vasoconstrictor, angiotensin II, thereby improving blood flow and blood pressure.
ACE inhibitors made by drug companies have been found to be beneficial in treating hypertension, particularly in patients with type-1 or type-2 diabetes, and also appear to provide good cardiovascular and renal protection. They do however have side effects.
After three months of intervention, Dr. Geerlings and his co-workers report that the hydrolysate casein group had a systolic blood pressure (SBP) 15 mmHg lower than the control group. Long-term captopril administration was association with a 25 mmHg reduction in systolic blood pressure.
"In Puleva Biotech we have identified several bioactive peptides from beta casein from goat milk that are Angiotensin Converting Enzyme inhibitors," Dr. Geerlings told NutraIngredients. "A hydrolysate rich in these peptides partially prevented high blood pressure in spontaneaous hypertensive rats (SHR).
"During a 3 months feeding study we demonstrated that rats consuming this hydrolysate had significantly lower blood pressures than a control group of rats."
Geerlings confirmed that the company filed a PCT patent several years ago giving them protection for the peptides, the hydrolysates containing these peptides, their use, and their production.
Interestingly, the researchers also report that beta-CN f78-83 was capable of passing a Caco-2 monolayer, a test of the absorption of compounds across the intestinal cell barrier, and suggesting that, unlike the other two peptides, this one was absrobed without significant digestion.
"However, further experiments are required to test if beta-CN f78-83, fragments thereof, or other peptides generated by digestive enzymes are responsible for the SBP-lowering effect," said the researchers.
The results of the human trial are expected by mid 2007, and Geerlings confirmed that the company could then launch the beta-caseins as an ingredient and in a finished product, most probably dairy (yoghurt).
Indeed, the caseins in a prototype yoghurt drink have excellent stability, he said.
Although cow's milk is the most commonly consumed milk in the West, on a worldwide basis goat's milk is believed to be drunk by more.
The work follows a recent study that reported that hydrolysed whey protein from cow's milk could lower blood pressure in hypertensive people.
Milk proteins - both caseins and whey proteins - have previously been shown to significantly reduce blood pressure in animal models, and the new study published in the November issue of the The Journal of Clinical Hypertension (Vol. 8, pp. 775-782), reports similar results in a small group of hypertensive humans.
Source: Journal of Dairy Science, 2006, Volume 89, Number 9 "Identification and characterization of novel angiotensin-converting enzyme inhibitors obtained from goat milk", A. Geerlings, I.C. Villar et al.
