Liver toxicity may not be the cause. Inflammation may be the culprit, which can lead to an abundance of symptoms, including fatigue and general malaise
The terms toxicity, in general, and liver toxicity specifically are used commonly by doctors and patients when describing an unhealthy biochemical state. Many doctors promote liver detoxification as a way to eliminate the cause of aches, pains, fatigue, headaches, sinus congestion, digestive problems, asthma, skin conditions, and a host of other maladies. It is even suggested that fatigue after a meal is due to a state of toxicity.
Proposed methods of liver detoxification include a restrictive diet, herbal supplements, and rice protein powder supplements. The use of these nutritional applications is purported to eliminate built up toxins by speeding up liver activity, which then allows for the reduction of the multifarious symptoms that are supposedly associated with liver toxicity.
Doctors should be aware that no reliable data supports this view of liver toxicity and detoxification.
Normal immune function versus liver toxicity. The acute phase response (APR) or sickness response is an excellent example to use to put the notion of liver toxicity in proper perspective. During the winter months we use the term flu to describe the APR; during the nonflu season, we use the term bad cold. The following signs and symptoms represent an APR, they occur in humans and have been induced experimentally in laboratory animals: generalized pain and tenderness, fever, increased sleep, decreased appetite, shivering, chills, malaise, somnolence, depression, and memory loss.1–3
When a patient comes down with an APR, it is not uncommon for a doctor to assume that the patient has developed liver or body toxicity and a subsequently depressed immune system. In fact, it is the immune system that generates the APR and not a toxic liver. In other words, an actively functioning immune system is required to generate an APR—not one that is depressed.1-3 The congestion and related coughing, sneezing, and nose blowing involves the stimulation of mucus production by various inflammatory mediators that are released by active immune cells.3
When a patient presents with APR, you should be thinking that peripheral inflammation is responsible for the symptoms. The main question in your mind should be: Is the peripheral inflammation due to infection or due to a combination of stressors that may be mental, physical, and nutritional?
How does peripheral inflammation lead to acute phase symptoms? Somatic (joints, muscles, etc) tissues are innervated by group III and group IV afferent/sensory fibers that alert the CNS about the biochemical state of the peripheral tissues. Additional sensory input regarding peripheral biochemistry occurs via the vagus nerve’s sensory receptors called paraganglia, which are located throughout the thorax and abdomen.1,2
Doctors should be aware that between 70% and 90% of vagal fibers are sensory, not motor.1 This is an important point that contradicts what we learned in neuroanatomy classes. We only learned the motor functions of the sympathetic and parasympathetic nervous systems in the various charts and tables that contrasted the opposing functions that each system has on various organs. We were never taught about the sensory fibers that begin throughout our abdomen and thorax and travel in the vagus nerve. Or at least these sensory fibers were never discussed in a fashion that alerted us to important clinical issues related to health and wellness.
Interleukin-1 (IL-1) is an example of a mediator that is released by active white cells and known to drive the acute phase response.1-3 Tumor necrosis factor (TNF) and interleukin-6 (IL-6) also induce the APR.1 IL-1, IL-6, and TNF are all members of a group of molecules called cytokines. All inflammatory mediators are likely able to drive the APR; however, IL-1 has been the more studied chemical. Prostaglandin E2 is also well studied and is known to cause fever, which is a component of the acute phase response.4
The APR can be induced in animals when IL-1 is injected into the periphery and administered to the hypothalamus.1 Further research showed that by performing a subdiaphragmatic vagotomy prior to the administration of IL-1, the APR could be abolished,1 which indicated that induction of the APR is dependent on hypothalamic activation by the peripherally administered cytokine.
In summary, it is the central nervous system that drives the expression of the APR, ie, cytokines and the inflammatory process stimulate group III and group IV afferents from musculoskeletal tissues and vagal afferents located in the thorax and abdomen, which ultimately leads to hypothalamic stimulation and the subsequent APR.
What about people who generally feel ill and suffer chronically with malaise and fatigue? They are likely to have a chronically active inflammatory state that is driven, in part, by an overactive immune system and not one that is depressed.
Do your patients feel tired after eating? A popular assumption made by alternative practitioners is that fatigue after eating equates with liver toxicity and/or other conditions, such as food allergies or yeast infection with Candida albicans. None of these are likely causes of fatigue. Believe it or not, assuming that a patient sleeps 6 to 8 hours per night, daytime fatigue may largely be an expression of inflammation.
Injections of either IL-1 or TNF into experimental animals has increased sleep in every species tested thus far. For example, when rabbits are given IL-1 at the onset of darkness, they sleep 3 extra hours during the first 12 hours after injection. These cytokines promote sleep whether administered directly into the brain, or following intraperitoneal or intravenous injections.5
One of the factors that determines how much we sleep is food intake. An excess of sleep occurs when there is increased feeding.6 In fact, overeating promotes cytokine release, which is thought to promote postconsumption fatigue.
Researchers fed rats what they called the cafeteria diet that consisted of bread, shortbread cookies, and chocolate. They discovered that the rats essentially gorged themselves like humans and then went to sleep. Their conclusion was that these foods did not cause liver toxicity. The researchers discovered that IL-1 levels rise in rats that pigged out on cafeteria food, compared with those that ate regular rat chow, and that cytokine elevations induced sleep.7 The same researchers fed the cafeteria diet to control rats and to rats that were given a subdiaphragmatic vagotomy, and discovered that only the control rats slept after overeating.6
From a clinical perspective, this research suggest that your tired and fatigued patients are not toxic, but are overfed, which subsequently creates inflammation and fatigue.
What are the dietary factors that may promote the acute phase response? Educate your patients to stop eating when they begin to feel full. No one should feel bloated and stuffed after eating. If you do, it means you overate.
In the remainder of this section, we will briefly consider foods that increase cytokine and prostaglandin release, which can subsequently promote inflammation and potentially induce the acute phase response.
Hyperglycemia is caused by foods with a high glycemic index, which means all foods that consist largely of refined flour and sugar. In this regard, a recent study indicated that hyperglycemia acutely increases circulating cytokine concentrations, in particular, IL-6 and TNF.8 At this point, you can conclude that patients should eat moderate amounts of whole foods (fruits, vegetables, fish, meat, and chicken) to avoid overeating and hyperglycemia that cause the APR.
Specific foods that may drive cytokine and PGE2 release and the subsequent acute phase response are those that are rich in omega-6 fatty acids.9 All grains, pastas, cereals, and store-bought salad dressings and most seeds, nuts, and packaged foods contain only omega-6 fatty acids. These foods must be dropped from the diet, save for nuts that can be consumed in modest amounts. Eat fruits and vegetables in place of the above-mentioned foods.
Magnesium deficiency is capable of promoting the APR. Animal studies have shown that magnesium deficiency promotes peripheral inflammation and nervous system hyperexcitability.10 This issue is of concern as the majority of Americans consume significantly less than the RDA for magnesium.11 To get more magnesium in your diet, eat lots of fruits and vegetables, and take a magnesium supplement—about 500 mg per day is sufficient for most. Additional supplements that can help to reduce inflammation and improve tissue health include fish oil, a multivitamin/mineral, coenzyme Q10, ginger, garlic, and proteolytic enzymes.
David R. Seaman, DC, MS, DABCN, DACBN, FACC, is an assistant professor at Palmer College of Chiropractic, Port Orange, Fla, and on the postgraduate faculties of several chiropractic colleges. He presents postgraduate seminars for chiropractic colleges and associations, is a clinical nutrition consultant, has written a textbook on nutrition, and published several articles in JMPT. Seaman can be reached via e-mail: docseaman@mac.com
References
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2. Watkins LR, Milligan ED, Maier SF. Immune and glial involvement in physiological and pathological exaggerated pain states. In: Dostrovsky JO, Carr DB, Koltzenburg M, eds. Proceedings of the 10th World Congress on Pain. Seattle, Wash: IASP Press; 369–385.
3. Contran RS, Kumar V, Collins T, Robbins SL. Robbins Pathologic Basis of Disease. 6th ed. Philadelphia, Pa: WB Saunders, 1999:74,86,714.
4. Blatteis CM, Sehic E. Pyrogen sensing and signaling: old views and new concepts. Clin Infect Dis. 2000;31(suppl 5):S168–177.
5. Krueger JM, Obal F, Fang J, Kubota T, Taishi P. The role of cytokines in physiological sleep regulation. Ann NY Acad Sci. 2001;933:211–221.
6. Hansen MK, Kapas L, Fang J, Krueger JM. Cafeteria diet-induced sleep is blocked by subdiaphragmatic vagotomy in rats. Am J Physiol. 1998;274:R168–174.
7. Hansen MK, Taishi P, Chen Z, Krueger JM. Cafeteria feeding induces interleukin-1 mRNA expression in rat liver and brain. Am J Physiol. 1998;274:R1734–1739.
8. Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, et al. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation. 2002;106:2067–2072.
9. Simopoulos AP. Essential fatty acids in health and chronic disease. Am J Clin Nutr. 1999;70(3 suppl):560S–569S.
10. Durlach J, Bac P, Bara M, Guiet-Bara A. Physiopathology of symptomatic and latent forms of central nervous system hyperexcitability due to magnesium deficiency: a current general scheme. Mages Res. 2000;13(4):293–302.
11. Ford ES, Mokdad AH. Dietary magnesim intake in a national sample of US adults. J Nutr. 2003;133(9):2879–2882.
12. Seaman DR. The diet-induced proinflammatory state: a cause of chronic pain and other degenerative diseases? J Manipulative Physiol Ther. 2002;25(3):168–179.
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