For about a decade, some people eating pine nuts have reported a range of adverse effects collectively known as pine nut mouth or pine nut syndrome (PNS). Simply put, pine nuts appear to be leaving a bad taste in the mouth of some folks. The medical term for this is cacogeusia, or specifically metallogeusia, which is a perceived metallic or bitter taste. We have all tasted bad or spoiled food at some time, but the curious wrinkle to pine nut mouth is that it often appears days later, sometimes lasting for weeks.
Since toxicology is the science that deals with the adverse effects of chemicals, it is appropriate to explore this somewhat puzzling case with the tools of forensic food toxicology. Unlike the world of mystery dramas in books, film, and television, solutions to mysteries in science rarely show themselves within the time it takes to cook a pine nut pesto fettuccine. It is, however, helpful to invoke the deductive skills of Sherlock Holmes to try to understand the curious case of the epicurean nut. In the words of the great detective, the game is afoot!
So what do we know? The foodie and medical self-help blogosphere has experienced a significant uptick in “me-too” reports of pine-nut mouth. Raw, cooked, and processed nuts all seem to be associated with problems. There have been a few published clinical reports of patients who have eaten pine nuts and found themselves in a doctor’s care (Mostin, 2001). A January 2010 case report in the Journal of Medical Toxicology calls PNS a possible “emerging problem” and describes a range of reported symptoms including bad tastes, nausea, and abdominal cramps (Munk, 2010). Anecdotal comments posted online also seem to detail episodes of residual food aversion and the experience of normally tasty foods, like hot cocoa, becoming horrible. The condition appears to self-resolve in time, apparently without long-lasting health effects.
Dealing With Adversity
PNS is in the general category of adverse food reactions broadly defined as a clinically abnormal response to food or food additives. Adverse food reactions include food allergy, food intolerance, and food sensitivity. About a third of us report we have a family member with adverse food reactions even though the actual number is probably much lower. For a particular food, some subpopulations or ethnic groups are more sensitive than others. We are all familiar with food allergies such as peanut allergy. In allergic people, pine nuts can trigger an immune reaction, and the response can be like that of peanut allergy or other common food allergens. The cascading immune reactions in a food allergy may include hives, welts, swelling, vomiting, diarrhea, and respiratory distress possibly leading to a generalized anaphylaxis that requires emergency medical attention. Researchers have identified a few proteins in pine nuts that can cause this life-threatening allergic reaction in those with diagnosed pine nut allergy (Hipler et al., 2004).
The clinical observations of PNS do not track well with pine nut food allergy symptoms as described in the medical literature, so then let us explore another type of food reaction known as food intolerance. Food intolerance often results from a metabolic disorder. The best example is people who are lactose intolerant; Hippocrates of ancient Greece first described this malady. These dairy product–sensitive folks have a metabolic disorder, sometimes because of aging, that limits the production of the digestive enzyme to process the lactose in dairy products. Left to the action of intestinal bacteria, the gaseous by-products of bacterial lactose digestion produce the characteristic bloating, cramps, and other uncomfortable effects experienced by the lactose intolerant after eating dairy products. Lactose intolerance is a well-studied metabolic disorder. Could pine nut syndrome be a similar metabolic disorder? The list of foods with the potential for metabolic disorders is long and includes common foods such as chocolate, some fruits, beets, some beans, and red wine. It is possible that PNS is a metabolic enzyme deficiency–related food disorder. However, people have been eating pine nuts for a long time, and we have not really heard much about PNS, even in recent history. The long-lasting effects of PNS in some people, well beyond times required for processing in the intestinal tract, would seem to argue against a metabolic disorder.
So where are we left? We fall to the category of food sensitivities called idiosyncratic reactions or individual hypersensitiveness. Another way to say this is that our personal genetic oddness can be responsible for our individual reactions to different foods. If we categorize PNS in this group of idiosyncratic reactions, it would have the company of celiac disease, sulfite sensitivity, aspartame sensitivity, and sensitivity to a range of other foods and food additives. A key concept is that there is a range of sensitivity, and some people experience a greater and often less-tolerable level of adverse reaction to a food. Often, we do not know the precise mechanism of idiosyncratic food sensitivities, and at this point, we certainly do not know the mechanism of PNS.
Bad Taste and Regulatory Science
The UK Food Standards Agency and the U.S. Food and Drug Administration have started collecting data on PNS although bad taste may not be a food safety issue. The French food safety authority (AFSSA) released a preliminary report late in 2009 that attempted to collect available knowledge about PNS (AFSSA, 2009). Although detailed data is lacking, there have been 800 reported cases of PNS in France since 2001. There is a high degree of variability in the description of symptoms, in the range of pine nut dose to induce effects, and in the duration of PNS. This is consistent with idiosyncratic food sensitivity. The AFSSA report briefly reviews some of the natural and synthetic chemicals that can taste bitter, noting that no analysis in their regulatory food safety screening has detected evidence of chemical, mold, or bacterial contamination in pine nuts related to PNS cases. There have been some similar tests performed by organizations in the pine nut trade or clinical diagnostic laboratories in PNS case follow-up, with similar negative or nonconclusive results.
The scientific sleuthing and range of laboratory tests involved in forensic toxicology can often exceed the requirements for food safety regulatory screening. While to date there has not been a pattern of detection of contamination by chemicals like heavy metals, pesticides, pathogenic bacteria, or molds and their mycotoxins in pine nuts, we have to respect that perhaps we have not been looking for the right toxic agent. Real toxicology is rarely as simple as television depictions such as those portrayed on CSI episodes. Perhaps the strongest argument against a toxic chemical or pathogenic microbial contamination is the apparent PNS incidence in several Western countries across a diverse international pine nut production and distribution chain. Contamination is possible, but source and distribution diversity in the pine nut production system discount this potential.
Several recent scientific papers and the French report cite changes in pine nut production and distribution as a possible link to PNS (AFSSA, 2009; Destaillats et al., 2010; Munk, 2010). To explore this, we have to explore what exactly a pine nut is. A pine nut is not a nut at all; it is a seed. Pine seeds come from the cones of various pine tree species in the Pinus genus. There are between 100 to 150 pine species worldwide. In recent times, demand has exceeded local production in many areas, and exports into the world market, principally from China, Pakistan, and Turkey, have increased significantly. The Food and Agricultural Organization of the United Nations (FAO) lists 29 Pinus species seeds used as food in common and indigenous peoples’ diet (FAO, 1998). FAO documents the use of pine nuts from ancient history to its current use as a foodstuff and a source of food oil. The major nutritional components of pine nuts include protein, fats, and carbohydrates. Like many other nuts and seeds, the approximate 30–70% oil content in pine nuts mostly includes those unsaturated fats regarded to be nutritionally good fats (Wolff and Bayard, 1995).
With the recent milk adulteration episode in China, there is concern expressed in the published scientific reports, including the French report, about similar contamination problems in Asian pine nuts. The contamination problem cited, however, quickly shifts to a problem of pine species contamination. With well over 100 pine species across the globe and only 29 listed by FAO as foodstuffs, we do not have to be too imaginative to recognize that PNS might well be the result of a new species of pine nut recently introduced into the food system that crosses the line of edible to nonedible.
In January of 2010, Nestlé researchers reported a study of the botanical origins for a range of pine nuts, including a sample linked to an episode of PNS (Destaillats et al., 2010). Using the chemical fingerprint of the type of fats in the nuts, the scientists were able to isolate two Asian pine species known as Chinese white pine (P. armandii) and Chinese red pine (P. massoniana), neither of which are a common edible pine nut in Western countries. Chinese red pine, also known as Masson’s pine, is an important pine species for the production of rosin and turpentine. Pines produce a range of terpenoid compounds, such as the bitter compound abietic acid, and these compounds help protect seed-bearing pinecones from insect and fungal attack. Although FAO does not list Chinese white pine nuts in their edible pine nut compendium, the PNS patient sample in the Nestlé study contained this variety. The French food authority and the recent Journal of Medical Toxicology paper also discuss a link between Chinese pine nut species and episodes of PNS. At present, none of the data is conclusive, but the suspected PNS link of a particular pine species, perhaps newly introduced into the Western food system, is important and curious.
Chemicals of Nature
Different species of pine nuts can present different chemical compositions that reflect nutritional value; taste and smell sensory properties; cooking and processing properties; and the toxic or health-enhancing effects of the peculiar types of secondary or trace chemicals found in every plant foodstuff. The Nestlé study examined the fatty acid profiles of different pine nuts and found that the Chinese varieties were not substantially different, and thus the lipid fraction of the pine nut is an unlikely agent of PNS. Nut oils can turn rancid, and this will affect taste, edibility, and potential toxicity. Harvest practices, shelling, processing, packaging, and exposure to light and air over time contribute to the oxidation of nut oils. Studies of the oxidation of pine nut oil show that its oxidation properties are not very different from other nut oils, and probably not different enough to present a syndrome unique in nuts (Miraliakbari and Shahidi, 2008).
It is possible that rancidity plays a role in PNS, but the delayed onset and long-lasting nature of the metallic or bitter taste sensation is not consistent with common experiences found with consumption of rancid vegetable oils that include the foul smell of the chemicals formed by lipid oxidation. Thus, as a premise in our deductive analysis, it is unlikely that product rancidity is a strong factor in PNS. The irritating terpenoid compounds found naturally in pines may play a role in the adverse response if these compounds occur in significant levels in new varieties of pine nuts used as food.
There are a wide variety of bioactive chemicals in plants and their seeds, and the medicinal uses of herbs and plant extracts are familiar to most people. Pine nuts are no exception. For example, pinolenic acid is a polyunsaturated fat in pine nuts that stimulates the enteroendocrine system to produce the hormone cholecystokinin (CCK) (Hughes et al., 2008). The levels of pinolenic acid in the range of pine nuts studied by Nestlé are not particularly different; however, the presence of this bioactive chemical and others found in typical and common dietary species of pine nuts may be significant. For example, in 2008, Dutch researchers showed that oil from the Korean pine nut (P. koraiensis) was eight-fold more potent in releasing CCK than Italian stone pine nut (P. pinea) (Pasman et al., 2008). The release of CCK tells the brain you are full, and so it is valuable for appetite suppression. We produce CCK in the upper part of the small intestine, and it stimulates the production of digestive enzymes, slows emptying of the stomach, and causes a contraction of the gall bladder to release bile into the lower part of the stomach called the duodenum, while increasing the production of bile in your liver. Bile aids in the digestion of fats.
In medical terminology, pine nuts are choleretic (increases bile production) and cholagogic (increases bile release from the gall bladder into the duodenum). Research originally published in 2005 and reviewed in 2008 shows a particular hormone, called FGF19 in humans and FGF15 in mouse models, is produced in the small intestine and that it can similarly regulate bile production (Inagaki et al., 2005; Jones, 2008). It is still too early in the research cycle to know if the bioactive compounds in pine nuts directly affect FGF19; however, it is a good candidate for further study since pine nut fatty acids should be able to interact with fat-responsive chemoreceptors that influence bile production. Excess bile can cause the metallic, bitter taste noted in PNS, as well as the characteristic bile-green coloring of stool anecdotally reported by some people after consuming pine nuts. Thus, in our deductive logic, we have established a general premise that some species of pine nuts can enhance bile production and release, and, furthermore, the taste sensation in PNS is consistent with bile reflux.
The Bitter End
One of the more curious and diagnostically challenging aspects of PNS is the reported long-lasting bitter taste and food aversion dynamic, often as a delayed response. For our deductive analysis, we need to explore the neurobiology of taste. All of us are somewhat familiar with the sensory taste buds on our tongues. Bitter taste sensation is thought by evolutionary biologists to be a protection against eating toxic or harmful foods. Regardless of what you think about the toxic risks of our modern world, the plants and animals in nature have developed an impressive arsenal of highly potent, interspecies chemical warfare agents that assist in their overall survival. Many of the most toxic natural products have a distinctive bitter taste for humans. When foods contain desirable tastes, such as sweetness, mixed with undesirable tastes such as sour, we sometimes have to overcome our neurobiology to “acquire” a taste for that food type. A bad taste experience with a particular food is a key formative process in the development of food aversion, and for some, this neurological conditioning can make just the thought of a particular food inspire the vomit reflex.
The neurobiology of taste is even more complex than you thought, because taste is not only on the tongue. Research in the past decade has shown the presence of taste receptors in the gastrointestinal tract (GIT) (Wu et al., 2002). “What’s that?” you say, “taste in my gut?” At the risk of ruining the experience of your next meal, we need to explore this curious sensory dynamic. We now know that we have bitter taste receptors, similar to taste buds, in our GIT. Science can often determine the “what” and “how” of nature, but it is often not well tasked to the “why.” Taste neurobiologists figure that if many toxic compounds in nature evoke a bitter taste, having these taste receptors in our gut provides an additional level of potential, taste-driven, “rejection and expulsion” of toxic food. Digestive and metabolic processes may, in fact, enhance the presentation of natural toxicants, and having a second line of defense would be good for survival. There is a cross wiring of the brain’s neurological sensation of tongue bitter and GIT bitter; thus, you may not realize that apparent bitter taste in your mouth is really the taste in your gut. That is a little unsettling for most of us to imagine.
In case reports of PNS, the taste disturbance can last for weeks. It is straightforward to speculate that bioactive compounds in some species of pine nuts have a more pronounced choleretic and cholagogic response leading to bile reflux and direct tongue bitter taste or, alternatively, that the bioactive compounds directly stimulate bitter taste receptors in the gastrointestinal tract. Nevertheless, we still need a premise in our deductive approach to explain the long-lasting effects, well beyond digestive cycle times, experienced by some with PNS. One explanation can be the sensitivity of bitter taste receptors to some of the particular bioactive compounds and their digestive metabolites in certain pine nuts, perhaps with a residual memory effect. Our current understanding of taste receptor neurobiology does not account for a similar absence-of-stimuli, “ghost limb” sensation experienced by amputees, but there may well be answers found in future psychophysics research about taste receptors and their long-term memory interactions with chemicals in food.
What Goes Around Comes Around
A quirk of human digestive biology may be one of the most important dynamics in our deductive process to explain PNS. First, we need to review some anatomy and physiology. When we eat, the nutritional building-block molecules of life are absorbed in our digestion system. The absorbed molecules get a quick push by the blood stream directly to the liver so it has a “first-pass” ability to metabolize nutrients and engineer many of the complex proteins, enzymes, and biochemical substrates required by our bodies. The liver also uses this first-pass to detoxify potentially toxic compounds and set them up for elimination. One process the liver uses to remove waste products and metabolites is through bile ducts, along with the components of bile, allowing the gall bladder to release the processed metabolites back into the digestive tract for fecal elimination. We call this biliary excretion. The release of bile fluids happens through a small nipple, wonderfully named the Ampulla of Vater, which lies in the duodenum, the transition between your stomach and small intestines. Remember that the big action of nutrient and other chemical absorption happens in the next 20 feet of the small intestine, so there is plenty of opportunity for some chemicals or metabolites previously processed by the liver to be reabsorbed and returned to the liver via the portal vein, for yet another pass by the liver. We call this remove-recycle-repeat process enterohepatic recirculation (EHR).
We know EHR can dramatically extend the residence time of some chemicals or drugs in the digestive tract, and, for toxic compounds, there is a potential for enhanced toxicity, especially liver toxicity. There are a good number of known, possibly toxic compounds in various pine species, and some additional laboratory detective work may help isolate the specific offender responsible for PNS. The potential for adverse interaction of pine nut chemicals with other foods or pharmaceuticals is also possible. It does not require too much imagination to develop a PNS deductive premise that a bioactive molecule or group of molecules in some pine nuts undergoes EHR. The recirculation of such a chemical or its metabolite may trigger the choleretic and cholagogic response we have discussed, or possibly the GIT bitter taste receptor in a direct manner, leading to the observed delayed or extended dynamic of the syndrome. Numerous other indirect mechanisms of PNS triggering could also involve EHR. Thus, we have a final premise to our deductive process that some natural chemicals in some pine nuts may have extended GIT residence time, and presumably extended opportunity for adverse effects, because of EHR.
A Holmesian Deduction
So we have a set of premises, perhaps some weaker and some stronger, to perform our Holmesian deduction on the curious case of the epicurean nut. We can deduce that PNS is an idiosyncratic adverse food sensitivity arising from a bioactive natural chemical or group of chemicals in a newly introduced dietary pine nut species. This chemical or group of chemicals is choleretic and cholagogic, or reactive with the bitter taste receptor of the gastrointestinal tract, and capable of enterohepatic recirculation. Sherlock Holmes’ compelling deductive powers would weaken the resolve of the most diabolical criminals into confession. In science, we use that similar deductive approach to formulate testable hypotheses, and the confession lies only in the data of well-designed experiments. Scientists are a unique breed of detective, and this and other PNS hypotheses will rise or fall on the data produced in future research.
For those who have experienced PNS, avoiding pine nuts is advisable, since your dietary “oddness” is much like my left-handedness and the continuing frustration of right-handed scissors. For those experiencing PNS, pine nuts can be uncomfortably toxic. Pine nut syndrome demonstrates in a clear way our special individual relationship to food. As we move farther and farther away from the production side of food, we rely more and more on a system of reliable strangers to grow, process, and prepare our food. It is important for this system to be responsive to quality concerns about the introduction of what may be an inedible species of pine nut into the food chain. At the end of the day, we as individuals are responsible for what we eat. Choose wisely.
ABOUT THE AUTHORGregory Möller, Ph.D., is Professor, University of Idaho-Washington State University School of Food Science, Moscow, ID 83843-2312
AFSSA. 2009. Information regarding reports of bitter taste following consumption of pine nuts. Request no. 2009-SA-0166:1-2. Agence Française de Sécurité Sanitaire des Aliments, Maisons-Alfort.
Destaillats, F., Cruz-Hernandez, C., Giuffrida, F., and Dionisi, F. 2010. Identification of the botanical origin of pine nuts found in food products by gas-liquid chromatography analysis of fatty acid profile. J. Agric. Food Chem. 58(4): 2082-2087.
FAO. 1998. Seeds, Fruits, and Cones. Chpt. in “Non-Wood Forest Products from Conifers,” Food and Agriculture Organization of the United Nations, Rome, Italy.
Hipler, U.C., Spoo, J., Elsner, P., and Bauer, A. 2004. Anaphylaxis after ingestion of pine nuts. Allergologie 27(11): 462-467.
Hughes, G.M., Boyland, E.J., Williams, N.J., Mennen, L., Scott, C., Kirkham, T.C., Harrold, J.A., Keizer, H.G., and Halford, J.C. 2008. The effect of Korean pine nut oil (PinnoThin™) on food intake, feeding behaviour and appetite: A double-blind placebo-controlled trial. Lipids Health Dis. 7(6): 1-10.
Inagaki, T., Choi, M., Moschetta, A., Peng, L., Cummins, C.L., McDonald, J.G., Luo, G., Jones, S.A., Goodwin, B., Richardson, J.A., Gerard, R.D., Repa, J.J., Mangelsdorf, D.J., and Kliewer, S.A. 2005. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab. 2(4): 217-225.
Jones, S. 2008. Mini-review: Endocrine actions of fibroblast growth factor 19. Mol. Pharmaceut. 5(1): 42-48.
Miraliakbari, H. and Shahidi, F. 2008. Oxidative stability of tree nut oils. J. Agr. Food Chem. 56(12): 4751-4759.
Mostin, M. 2001. Taste disturbances after pine nut ingestion. Presented at the XXXVIII Congress of the Society for Clinical Toxicology (abstract). J. Emerg. Med. 8(1): 76.
Munk, M-D. 2010. “Pine Mouth” Syndrome: Cacogeusia following ingestion of pine nuts (genus: Pinus). An emerging problem? J. Med. Tox. DOI: 10.1007/s13181-009-0001-1.
Pasman, W.J., Heimerikx, J., Rubingh, C.M., van den Berg, R., O'Shea, M., Gambelli, L., Hendriks, H.F.J., Einerhand, A.W.C., Scott, C., Keizer, H.G., and Mennen, L.I. 2008. The effect of Korean pine nut oil on in vitro CCK release, on appetite sensations and on gut hormones in post-menopausal overweight women. Lipids Health Dis. 7(10). DOI: 10.1186/1476-511X-7-10.
Wolff, R.L. and Bayard, C.C. 1995. Fatty-acid composition of some pine seed oils. J. Am. Oil Chem. Soc. 72(9): 1043-1046.
Wu, S.V., Rozengurt, N., Yang, M., Young, S.H., Sinnett-Smith, J., and Rozengurt, E. 2002. Expression of bitter taste receptors of the T2R family in the gastrointestinal tract and enteroendocrine STC-1 cells. Proc. Nat. Acad. Sci. 99(4): 2392-2397.