One of the common barriers to weight loss is the uncomfortable sensation of hunger that drives overeating and makes dieting fail, even in those who are obese from over-consumption of calories. Over the past two decades we have worked closely with approximately twenty thousand patients in a private suburban family practice in New Jersey specializing in nutritional interventions for weight loss and disease prevention/management. Our experience is that enhancing the micronutrient quality of the diet even in the context of a substantially lower caloric intake dramatically mitigates the experience of hunger. A diet high in micronutrients appears to decrease food cravings and overeating behaviors. Sensations such as fatigue, weakness, stomach cramps, tremors, irritability and headaches, commonly interpreted as "hunger", resolve gradually for the majority of people who adopt a high nutrient density diet, and a new, less distressing, sensation (which we label "true" or "throat" hunger) replaces it.

It is well documented that a diet low in antioxidant and phytochemical micronutrients leads to heightened oxidative stress and a build-up of toxic metabolites [1–4]. It has also been shown that a higher intake of nutrient rich plant foods decreases measurable inflammatory by-products [5–10]. Our hypothesis is that a diet containing an abundance of processed food and low in micronutrient-rich plant foods can create physical symptoms of withdrawal when digestion ceases in between meals. Our contention is that during the catabolic phase of the digestion and refeeding cycle, when digestive activities cease, these withdrawal symptoms, misperceived as "hunger", develop from a diet that is inadequate or poor in micronutrients. We call these symptoms "toxic hunger". It is our clinical experience that such withdrawal symptoms drive overeating behavior and are a major factor leading to obesity. There is significant support for our observation and hypothesis, yet a relative lack of research on the determinants of overeating behavior and the hunger drive. A "dopaminic high" [11, 12] from ingestion of high calorically concentrated sweets and fats has been documented and leads to subsequent craving of these foods. Very little human research has been done in this area.

In this investigation we were interested specifically in exploring the effect of a high nutrient density diet on participants' perceptions of hunger. We speculate that the discomfort of withdrawal from the toxins mobilized when one tries to refrain from consumption of pro-inflammatory processed foods and animal products may be also be a major contributor to compulsive eating and consequent obesity. Dietary micronutrients such as antioxidants and phytonutrients are required for the body to properly reduce the production and removal of metabolic waste products. In counseling patients to increase their micronutrient intake from greens and other nutrient-rich plant foods, our experience is that healthful eating is more effective for long-term weight control because it modifies and diminishes the sensations of withdrawal-related hunger, enabling overweight individuals to be more comfortable even while consuming substantially fewer calories.

In an attempt to further explore and validate our clinical observations, we conducted an internet-based survey of 768 individuals who had changed from the previous usual diet to a high nutrient density diet. The participants were recruited from a physician-run website of approximately 4000 subscribers designed to support the shift to a high nutrient density diet. In the survey we investigated the relationship between dietary micronutrient density and the symptoms of hunger.

This study provides important insights into hunger in a society characterized by over-consumption of processed food with an excess of calories and deficiency of micronutrients. Such hunger creates a cycle of overeating leading to obesity and is an obstacle for those who attempt to establish a healthy eating pattern and normal BMI. We found highly significant differences in the experience of hunger on the high nutrient density diet compared to the previous usual diet in a large sample of people who had made the shift to a diet high in micronutrients and lower in calories. The uncomfortable physical and emotional symptoms of hunger were much less prevalent after a change to the high nutrient density diet was made. We also observed a "dose response" that was strongly correlated with the degree of adherence to the high nutrient density diet. Our findings reveal that those who are able to make the change to a high nutrient density diet experience uncomfortable sensations of hunger less often than they experienced on their previous usual diet. In this survey of 768 participants, over 75% indicated that they observe the high nutrient density diet most or all of the time. Participants who adhered to the high nutrient density diet overall found hunger to be an uncomfortable experience less often; this may explain the previously reported high levels of compliance and successful weight loss [18] with the high nutrient density diet. Their hunger was less often characterized by classic withdrawal symptoms such as headaches, tremors, stomach cramps, and mood changes. Rather, it was more often felt as a throat sensation that was easily tolerated.

As soon as the intake, digestion and assimilation of food is complete, the catabolic utilization of glycogen reserves and fatty acid stores begins. Hunger normally increases in intensity as glycogen stores are diminishing toward the end of glycolysis, and should not occur at the start of the catabolic phase when glycolysis begins (see Figure 10). It is our contention that uncomfortable symptoms that drive overeating behaviors early in the catabolic phase should be recognized as withdrawal symptoms from a sub-optimal diet and not true hunger. After the completion of digestive activity, during catabolism, the mobilization and elimination of cellular waste products are heightened, thus precipitating symptoms commonly thought to be hunger. In contrast, true hunger occurs much later when glycogen stores near completion, preventing gluconeogenesis. Gluconeogenisis is the utilization of muscle tissue for needed glucose once glycogen stores have been depleted. True hunger protects lean body mass, but does not fuel fat deposition. It exists to protect lean body mass from utilization as an energy source.

Recent research on the physiology of metabolism provides a plausible explanation for our findings. When a diet is low in dietary antioxidants, phytochemicals and other micronutrients, intra-cellular waste products such as free radicals, advanced glycation end products, lipofuscin, lipid A2E, and others accumulate [9, 19]. Other studies have demonstrated an adverse impact of low-micronutrient foods containing higher amounts of simple carbohydrates, fats and animal products on levels of inflammatory markers, metabolic by-products and oxidative stress in the body [20, 21]. It is well established in the scientific literature that these substances contribute to disease [22–25], and can be associated with typical withdrawal symptoms, including headaches [26, 27]. Heightened elimination of these waste products may create symptoms that can be experienced similarly to withdrawal from drug addiction [28]. In the absence of an adequate intake of phytochemicals and other micronutrients, cellular detoxification is impaired [29] which elevates cellular free radical activity, priming the body with more substrate to induce withdrawal symptoms when digestion ceases. Our theory is that these uncomfortable symptoms, relieved by eating which halts catabolism and arrests the detoxification process, are widely misperceived as hunger. In a society with an abundance of fast food and high rates of obesity, commonly experienced sensations of hunger may actually be symptoms of withdrawal from a diet that is inadequate in micronutrients. Such a diet creates an excess of pro-inflammatory metabolic waste products as well as an addiction syndrome. There is growing evidence that food addiction is a clinical pathological condition [30–43]. Our hypothesis, supported by this pilot study, is that this addiction is caused by withdrawal symptoms misread as hunger from pro-inflammatory foods and can be mitigated by consumption of a diet high in anti-inflammatory micronutrients found in vegetables and other micronutrient-rich plant foods.

Evidence suggests that overweight individuals build up more inflammatory markers and oxidative stress when fed a low nutrient meal compared to normal weight individuals [20, 21]. The heightened inflammatory potential in those with a tendency for obesity is marked by increasing levels of lipid peroxidase and malondialdehyde and reduced activation of hepatic detoxification enzymes [44]. This is supportive of our experience that people prone to obesity get more withdrawal/hunger symptoms, preventing them from being comfortable in the non-digestive (catabolic) stage where breakdown and mobilization of toxins is enhanced. The resulting uncomfortable symptoms drive them to eat again and over-consume calories. It is a vicious cycle promoting continuous (anabolic) digestion, frequent feedings and increased intake of calories. Chronically overweight people in the typical American food environment feel "normal" only by eating too frequently or by eating a heavy meal, so that the anabolic process of digestion and assimilation continues right up to the beginning of the next meal. In both cases, as our overweight patients report, excess calories are needed in order to feel normal. A review of research on companion animals suggested that the introduction of specific micronutrients positively influenced the health status of animals whose natural detoxification systems were compromised, and reduced the accumulation of inflammatory markers [29]. This may explain why those on the high nutrient density diet were able to go for longer periods without feeling "hunger" symptoms.

There exists only a small body of previous research exploring the relationship between the type of foods ingested and the intensity and/or frequency of hunger. One theory that has been investigated is the glucostatic theory which links dynamic changes in blood glucose with appetitive sensations [45–48]. Several studies have explored the relation between the glycemic index or fiber content of food and satiety, whereas others have examined whether the type or amount of fatty acids, sugars or protein in the diet affect the sense of hunger [49–62]. Results have been inconsistent. This may be due to the unknown variable of micronutrient intake in these studies. Some studies have documented a decrease in appetite with ingestion of greater amounts of fiber and/or micronutrients [49, 52, 56]. Recently, a Canadian study found that fasting and postprandial appetite ratings were reduced in women who were supplemented with multivitamins and minerals [63].

The findings of this study are particularly significant given the nature of the diet we studied. Highly significant reductions in blood pressure, LDL cholesterol, fasting glucose and body weight have been reported in persons who have made the change to a high micronutrient diet [18]. Further, there is a vast body of research documenting the protective benefit of a micronutrient-rich diet against cancer and cardiovascular disease [1, 8, 10, 24, 25, 64–77]. If clinicians can assure their patients with confidence that they will not experience uncomfortable sensations of hunger after the "detoxification" stage is over, they can keep their patients motivated to withstand the withdrawal symptoms they experience early in the dietary transition. The outcome will be not only substantial and sustainable weight loss, but prevention of many major chronic diseases in our patients. Our hypothesis clearly requires further study and testing, but this preliminary study justifies additional investigations into this interesting and significant issue.

We must acknowledge the limitations of this study, including the fact that this was a retrospective, non-controlled study. The instrument we used has not been validated on large or diverse populations, although we did establish preliminary internal consistency and content validity. We recognize that participants were self-selected and may have been biased in their responses by exposure to the information on the website and resources to which they all subscribed. There are discussions of "toxic hunger" versus "true hunger" in the written and web-based materials that participants had access to. Participants were, however, assured of the anonymity of their responses in the introduction to the survey, and the survey responses were received from the Survey Monkey website without any identifying information, including no inclusion of email addresses of those who completed the surveys. It will be important to see if this dramatic shift in hunger perception would be found in populations not exposed to "leading" messages in future studies. We also did not assess the actual diet that each participant typically maintained prior to changing to the high nutrient density diet, nor did we validate the self reports of degree of compliance to the high nutrient density diet. Future studies should include food diaries and measures of biomarkers to quantify these variables more precisely.

However, given these limitations, the number of participants and highly significant test statistics provide leads for future studies that are better controlled and prospective in design and some important clinical insights. Further studies should explore the physiological and neurohormonal correlates of "toxic hunger" and of "true hunger", including measures of oxidative stress and ghrelin levels in people who adhere to the high nutrient density diet and the previous usual diet. It would also be helpful to examine how long the typical "withdrawal phase" from the previous usual diet lasts as people shift to the high nutrient density diet. This information would be valuable in our clinical efforts to support those who are making the change to healthier eating patterns.

We found significant differences in the symptoms, location and unpleasantness of hunger on the high nutrient density diet compared to the participants' previous usual diet in a large sample of people who had made the shift to a diet high in micronutrients and lower in calories. Hunger is one of the major impediments to successful weight loss. Our findings suggest that it is not simply the caloric content, but more importantly, the micronutrient density of a diet that influences the experience of hunger. It appears that a high nutrient density diet, after an initial phase of adjustment during which a person experiences "toxic hunger" due to withdrawal from pro-inflammatory foods, can result in a sustainable eating pattern that leads to weight loss and improved health. Further studies are needed to confirm these preliminary findings that may have important implications in the global effort to control rates of obesity and related chronic diseases.