A reduction in systolic BP of only 2 mmHg may already result in a 6% reduction in fatal stroke, and a 4% reduction fatal coronary heart disease (CHD).
Knowledge on the effect of dietary protein, therefore, may have an important public health impact. A substantial body of evidence suggests a, possibly weak, beneficial effect of total dietary protein on BP, which may be most apparent in populations with elevated BP and possibly older populations. We cannot exclude, however, that this effect is due to a lower carbohydrate intake. In observational studies more often an inverse association was found for plant protein than for animal protein. The beneficial effect of protein, therefore, may be mainly due to protein from plant sources. Data on protein from specific sources are too scarce to draw any conclusions.
The aim of the current systematic review was to give a comprehensive overview of the evidence on dietary protein and human BP, published until June 2010. Papers were independently screened by 2 reviewers, and data of 46 studies were extracted using a predefined procedure. Several other reviews on protein and BP have already been conducted in the past.
However, the most comprehensive review of these is already 14 years old.
Furthermore, the present review is the first to focus on possible BP effects of different protein types and on sensitivity of population subgroups.
Several methodological issues of studies need to be addressed. First, in observational studies, even after extensive adjustment for potential confounders, residual confounding may exist from other nutrients associated with protein intake, or from energy, which is not only correlated to protein, but also to several other BP-determinants like exercise, BMI, and dietary pattern. It is difficult to say how much the remaining confounding from known or unknown nutrients that are correlated to plant or animal protein, have influenced the estimates in observational studies. Randomized controlled trials in which the effects of plant protein and animal protein are compared, keeping other nutrients constant, are needed. Second, a diet high in one type of protein (animal protein or plant protein) does not necessarily mean that the other protein type is replaced, as a diet may be high or low in both types of protein. Most of the observational studies investigating types of protein did not adjust their estimates for intakes of other protein types. In randomized trials these factors are more standardized.
Third, respondents in observational studies may be misclassified according to their self-reported protein intake, which may dilute the protein-BP association.
Fourth, for investigation of long-term effects of protein on BP, an observational study is the most suitable type of study, because of the costs of a trial. However, contrasts between high and low protein intake are often larger in trials than in observational studies. Short term effects of protein on BP can, therefore, be more easily detected in trials. Finally, all observational studies were conducted in the general population, whereas trials were more often conducted in selected populations that are possibly more sensitive to BP interventions. However, in several trials BP was the secondary outcome 
. If participants in these studies were not blinded for the results of the BP-measurements, bias may have been introduced, because awareness of BP may influence participants' lifestyle or other behavior.
The underlying mechanism for a potential beneficial effect of protein on BP has not yet been clarified. Several hypotheses have been put forward. First, dietary protein has been related to synthesis of cellular ion channels, which may indirectly influence the pathways in BP regulation.
High protein intake may induce natriuresis, leading to lower BP.
Second, experiments suggest that dietary protein or protein fractions could improve insulin sensitivity and thereby BP.
Third, dietary protein supplementation may result in a higher concentration of the amino acids tyrosine and tryptophan in regions of the brain or blood vessel wall, triggering a vasodilatory response.
The amino acid arginine, which is a substrate for nitric oxide, may play a role in vasodilatation, although it is unclear whether dietary intake of arginine is relevant in this respect.
Finally, as has already been stated in this review we cannot exclude that a lower BP is related to a lower carbohydrate intake instead of a higher protein intake.
In conclusion, evidence suggests a small beneficial effect of protein on BP, especially for plant protein. More data on protein from specific sources like dairy, grain or nuts and data in population subgroups should be obtained from epidemiological studies. Furthermore, there is a need for BP trials that focus on plant and animal protein and protein from specific sources. Preferably, these trials should be conducted in untreated (pre)hypertensive people. Finally, studies aimed at potential BP lowering mechanisms related to protein intake are warranted.