Dr. Joe Sebranek, Professor, Iowa State University, USA, (sebranek@iastate.eduk), April 2009.
Sodium and/or potassium nitrite has experienced a very long and somewhat checkered history as a meat curing ingredient and preservative. The first use of meat curing for preserving meat was undoubtedly done with nitrate and occurred so long ago that it has been impossible to determine when it actually began. However, there is written evidence that the Greeks and Romans utilized saltpeter (nitrate) as a meat curing agent. The best estimates available suggest that nitrite and nitrate have been used for some 5,000 years to cure and preserve meat. It is believed that meat curing with nitrate was first discovered as a result of adding salt contaminated with saltpeter (potassium nitrate) to meat and observing that, in addition to improved preservation, a unique color and flavor resulted from this process. The bottom line is that this process has been around for a long, long time.
The first true applications of science to meat curing became evident in 1822 when nitrate was first identified as an anti-botulism factor in cured meat. Somewhat later, in 1891, the first publication appeared reporting that nitrate-to-nitrite conversion was responsible for the preservation effects of cured meat. Then in 1899 and 1901, respectively, it was discovered that nitrite was the source of cured meat color and that nitric oxide was the active agent in forming cured meat color. It should be noted at this point that the meat industry “discovered” the importance of nitric oxide well over 100 years ago. Nitric oxide has, in only the past 20 years, become recognized as a very, very important compound in human physiology. The initial discoveries concerning nitrite and nitric oxide at the turn of the twentieth century resulted in several subsequent studies by the USDA and others in the early 1900s that resulted in establishment of the first USDA regulations in 1925. These regulations described appropriate use of nitrate and nitrite for meat curing. Following this, from the 1920’s to the 1950’s, researchers continued to refine curing processes by developing curing accelerators like ascorbate and erythorbate. The role of nitrite in cured meat was also clarified and shown to include the unique contributions of distinct flavor and a powerful antioxidant function in addition to the color and potent antimicrobial functions already recognized.
At this point, all was well.
However, in 1956, the first clouds appeared on the horizon when it was discovered that fish meal cured with very high concentrations of nitrite was responsible for inducing cancer in mink that were fed the fish meal. The cause was found to be n-nitroso compounds formed from nitrite and secondary amines in the fish meal. This resulted in extensive research in the 1960’s focusing on potential relationships between nitrite in human food, nitroso compounds and cancer in humans. Some nitroso compounds were found in cured meats, mostly in bacon and by the early 1970’s, there was serious consideration of banning nitrite from use in processed meats. However, research in the mid-1970’s showed that nitroso compounds in cured meat were not an issue with proper control of nitrite concentrations and meat processing conditions. Further, research in the late 1970’s discovered endogenous nitrate and nitrite in the human intestine and saliva, suggesting an important biological role for these compounds. This period of time turned out to be very important for two reasons; first, the extensive research and accompanying publicity on the relationship between nitrite and cancer resulted in firmly entrenched perceptions of cured meat as a contributor to human cancer that continue to this day, and second, the discovery of endogenous nitrite in the body was the forerunner to a subsequent major breakthrough in biology. The breakthrough came in 1986 when it was shown that nitric oxide was a major biological messenger molecule responsible for regulation of blood pressure and blood flow, neurotransmission and brain function, immune system function and wound healing. This turned out to be such a momentous discovery that the 1998 Nobel Prize for Physiology/Medicine was awarded to the three researchers who identified the critical biological role of nitric oxide.
The role of nitric oxide in control of blood flow and blood pressure means that nitric oxide has a potentially important role in cardiovascular health. One area where this may be important has been demonstrated in work with blood transfusions. Physicians have long been puzzled by the increased risk (~25%) of heart attacks and strokes following blood transfusions. Recent research has reported that collected blood shows a dramatic depletion of nitric oxide to 30% or less of normal levels within 24 hours. Research with dogs has shown that nitric-oxide-treated blood transfusions significantly reduced heart attacks (Reynolds et al., 2007).
However, the various contributions of nitric oxide to biological functions were not initially attributed to nitrite because the mechanism believed to be most important for nitric oxide formation has been the nitric oxide synthase (NOS) system. The NOS system generates nitric oxide by converting arginine to citrulline in the presence of oxygen. This system becomes limited in case of low oxygen such as restricted blood flow. Consequently, the current hypothesis is that tissue and blood nitrite provides a low-oxygen source of nitric oxide because nitric oxide is easily formed from nitrite. This would mean that nitric oxide may be a critical cardiovascular protective component when oxygen is limited such as the initial stages of heart attacks or stokes.
To test this hypothesis, researchers have been studying the effects of dietary nitrite on tissue concentrations of nitrite and on induced heart attacks in mice. They have found that dietary nitrite significantly reduced injury and increased survival from heart attacks (Bryan et al., 2007). They further suggested that dietary nitrite may be a critical component for cardiovascular health and that nitrite could part of the reason that vegetables have a positive impact on human health. Gladwin et al., (2005) concluded, “Most provocatively, these studies suggest that the cardio protective effects of leafy green vegetables could derive from nitrite, in addition to the often cited antioxidant effects of these food groups” and also suggested that “The solution to these problems should … lead to the potential consideration of nitrite as an “essential nutrient”…”. This is a complete, 180-degree change in thinking about nitrite and human health.
A recent comparison of the widely recognized Mediterranean diet, which is viewed as a healthful diet because of a low unsaturated fat intake, with a typical western diet showed the Mediterranean diet to represent about 10-12 fold greater nitrite/nitrate intake (Bryan, 2007). This led Bryan (2006) to ask “Could it be that the stringent regulations on nitrite/nitrate in drinking water and foods contribute to the contemporary diseases of today due to inadequate nitrite or nitrate in the diet…?”
Thus, nitrite has an important role in physiology and dietary nitrite appears to be protective against cardiovascular disease and injury (Mazzone and Carmeliet, 2008). It has been suggested that recommended dietary limitations on nitrate and nitrite be reconsidered for optimal health. This is a truly refreshing change in thinking about the role of nitrite in human health. Currently, there are several human clinical trials underway involving nitrite and much more information can be expected in the near future. Depending on the results of these trials, an extended effort to re-educate the public about the role of nitrite will be important in order to change current consumer perceptions.
References
- Bryan, N.S. 2006. Nitrite in Nitric Oxide Biology: Cause or Consequence? A Systems-Based Review. . Free Radical Biology & Medicine 41:691-701.
- Bryan, N.S. 2007. Dietary Nitrite and Nitrate Contribute to Cardiovascular Health and Disease. Proc. Meat Industry Research Conf., American Meat Science Association, Savoy, Il.
- Bryan, N.S., J.W. Calvert, J.W. Elrod, S. Gundewar, S.Y. Ji and D.J. Lefer. 2007. Effects of Dietary Nitrite and Nitrate on Myocardial Ischemia/Reperfusion Injury. Proc. National Acad. Sciences, Early Edition. www.pnas.org/cgi/doi/10.1073/pnas.0706579104.
- Gladwin, M.T., A.N. Schechter, D.B. Kim-Shapiro, R.P. Patel, N. Hogg, S. Shiva, R.O. Cannon III, M. Kelm, D.A. Wink, M.G. Espey, E.H. Oldfield, R.M. Pluta, B.A. Freeman, J.R. Lancaster Jr., M. Feelisch and J.O. Lundberg. 2005. The Emerging Biology of the Nitrite Anion. Nature Chemical Biology 1(6):308-314.
- Mazzone, M., and P. Carmeliet. 2008. A Lifeline for Suffocating Tissues. Nature 453(26):1194-1195.
- Reynolds, J.D., G.S. Ahearn, M. Angelo, J. Zhang, F. Cobb and J.S. Stamler. 2007. S-nitrosohemoglobin deficiency: A mechanism for loss of physiological activity in banked blood. Proc. National Acad. Sciences 104(43):17058-17062.