Maintaining adequate dietary intake of essential nutrients is fundamental to human health in general and liver health in particular. It is important to review current diets with patients in order to determine what foods they are eating and help them to develop an optimal diet that supports their health and liver function. In general, a physician or nurse should review with a patient what their general dietary intake is. Keeping food logs or online diaries can be very helpful to clarify what patients eat on a day-to-day basis.

In the context of liver health, maintaining good nutrition is essential for meeting the patient’s physiological requirements as well as providing additional psychological, spiritual, social, and cultural benefits. With this in mind, it is important to assess the specific needs of the liver transplantation patient, both before and after transplantation. Optimal body mass index and body metrics should be assessed and targeted as part of a nutritional evaluation. The health-care team should carefully address the specific caloric needs of each patient throughout the clinical course, in terms of the number and quality of calories.

In terms of the types of foods patients should eat, a diet that contains high amounts of excess sugars is typically regarded as an unhealthy diet. Energy-dense and nutrient-poor foods include refined sugars, candies, fried foods, and so-called junk food. The medical literature is consistent that eating such foods favors the onset of obesity, diabetes, and fatty liver disease, all of which have an impact on liver function and liver transplantation (Sarno et al. 2013; Corey and Kaplan 2014).

Red and processed meat consumption has consistently gained a reputation as a contributor to diseases such as cancer (Corpet 2011; Tang et al. 2012). The data also suggests that red meat, in particular, is proinflammatory and pro-carcinogenic. For example, the European Prospective Investigation into Cancer and Nutrition-Potsdam study of 2,198 men and women found that red meat consumption was significantly associated with higher levels of the inflammatory markers GGT and hs-CRP when adjusted for confounding factors related to lifestyle and diet (Montonen et al. 2012). However, it is important to ensure that patients continue to receive nutrients commonly found in meats such as iron, vitamin B, and essential amino acids. One report suggested that perioperative enteral and parenteral nutrition have benefits in reducing the morbidity and mortality of liver surgery (Masuda et al. 2013). In particular, branched-chain amino acids appear to promote protein and glycogen synthesis as well as improve immune system function. The administration of branched-chain amino acids, during the perioperative period, to patients undergoing hepatic resection improves liver function more quickly after surgery (Togo et al. 2005). The use of oral branched-chain amino acids might prolong the ability of the patient to wait for a liver transplant by preserving liver function in patients with cirrhosis (Kawamura et al. 2009). Thus, care should be taken to provide nutritional supplements when necessary to augment these requirements. There currently exist several high-quality protein supplements from vegetable sources that are commonly available.

Given the physiological response to liver failure and transplantation, considering diets that reduce inflammation might be helpful in the management of these patients. Inflammation itself is associated with high levels of oxidative stress that can damage both the body’s tissues and genetic material. In integrative medicine practice, there is a long tradition of utilizing diets with anti-inflammatory effects to reduce the negative effects of oxidative stress. Ancient cultures also developed and used anti-inflammatory diets, such as in the Ayurvedic medicine (a system of traditional medicine native to the Indian subcontinent that stresses plant-based treatment), which are now investigated using modern scientific methods (Sumantran and Tillu 2012). Proinflammatory foods are those that include refined sugars and starches, saturated fats, and trans fats while having low amounts of omega-3 fatty acids and other natural antioxidants (Giugliano, Ceriello, and Esposito 2006). Anti-inflammatory foods are those that include omega-3 fatty acids, natural antioxidants, and fibers found in fruits and vegetables (Giugliano et al. 2006).

Energy intake, energy density, and energy balance in the body are substantially affected by systemic inflammation. Targeting systemic inflammation is likely to be important in nutritional interventions in liver patients. Wholesome diets rich in fresh and cooked vegetables and lean protein are a usual part of the recommendation from our Integrative Medicine Center (Monti and Bazzan 2008). This combination of foods and appropriate supplements can have a profound anti-inflammatory effect in the gut and body (de Moreno-de LeBlanc et al. 2007; Abd El-Atti et al. 2009; Boleij and Tjalsma 2012). Achievement and maintenance of a healthy body composition via a plant-based diet high in low-glycemic fruits, vegetables, and whole grains and low in saturated/trans fats, red or processed meats, and added sugars/starches should be the guidelines provided to patients from their health-care providers.

As many as 50 % or more of patients take vitamins, herbal preparations, and other supplements, often without medical guidance (Wanchai et al. 2010). More specifically in the population of patients with liver disease, approximately one quarter to one third report taking some type of nutritional supplement (Strader et al. 2002; Ferrucci et al. 2010). This is important information for the clinician caring for the patient with chronic liver disease as well as those who are pre- or posttransplantation. Physicians need to be aware of the various supplements that might be beneficial in these patients as well as limit potential dangers such as supplement-drug interactions. There are a growing number of research studies upon which to develop a specific approach for utilizing nutritional supplements in patients who are undergoing liver transplantation. While taking supplements must be weighed against other medications that the patient may be on to ensure that there are no potentially adverse interactions, many food-based supplements are safe and can be used along with medications. The health-care provider needs to carefully follow the patient for any adverse effects or drug-supplement interactions.

Data support the use of supplements to provide nutritional support not obtained with the patient’s current diet. The goal for using supplements should be to ameliorate the specific pathophysiological stressors and support the needs of the patient. It should also be noted that good diets do not automatically supplement all aspects of nutrition adequately and therefore nutritional supplements can be considered in many patients. Correcting and augmenting nutritional needs might help address immune function, inflammation, and micronutrient status that can provide health benefits and possibly enable the patient to experience less complications from liver disease and the treatments, including transplantation.

A variety of nutritional supplements have been suggested to be helpful either for liver health or more specifically in the setting of liver transplantation patients. This section reviews the limited data on these supplements. A randomized controlled trial of immunonutrition enriched in n-3 fatty acids, arginine, and nucleotides evaluated 52 patients receiving immunonutrition and 49 patients receiving an isocaloric control diet beginning 5 days post-liver transplant (Plank et al. 2012). There were no significant differences in total body protein levels, rate of infectious complications, or length of hospital stay. Thus, supplementation with the immunonutrition did not affect outcomes in liver transplant patients postsurgery.

A small pilot study of 23 living donor liver transplantation patients were randomly assigned to either an experimental group who received a commercial supplement enriched with antioxidant nutrients for 5 days immediately prior to surgery or a control group (Nagata et al. 2013). Both groups maintained their usual diet. The results showed that the group receiving the supplements had an increased antioxidative capacity in their serum as measured by spectrophotometry using a free-radical analytical system. However, there were no significant differences in terms of nutritional parameters, liver function, immunological parameters, or postoperative outcomes.

CoQ10 is a cofactor for a number of energy-producing pathways within the cell. Generally, it is used to aid in energy production within the body and improve cardiac and immune function. Several studies have explored the use of Coenzyme Q10 in transplant patients.

An early study showed that donor rats or recipient rats which were given an intravenous infusion of CoQ10 1 h before liver transplant had significantly improved survival times, even when the transplanted liver was exposed to heat-related ischemic damage (Sumimoto et al. 1987). Untreated rats all died within 2 days, but almost half of the rats who had received CoQ10 survived at 1 week. Interestingly, it did not matter if the donor or recipient rat was treated with CoQ10 suggesting that once it accumulated in the donor, liver survival was improved along with reductions in liver enzymes.

Another line of evidence suggests that the related molecule, mitoquinone, may reduce inflammation and cell damage in hepatocytes in patients with chronic hepatitis C infection even though HCV levels did not change (Gane et al. 2010). The combination of antioxidants, such as idebenone, melatonin, and arginine were shown to almost completely protect rat hepatocytes from damage related to sodium nitrite-induced hypoxia (Ali et al. 2012).

Thus, while CoQ10 might help support the health of hepatocytes and protect them from various physiological insults, it is unclear whether CoQ10 would be helpful in human liver transplantation. Future studies would be needed to explore such a possibility.

Essential fatty acids are crucial to cellular functions throughout the body. Diets that are rich in omega-3 polyunsaturated fatty acids (ω3-PUFAs) such as alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid have been shown to be associated with lower incidences of several chronic diseases (Vanden Heuvel 2012). Omega-3 fatty acids have known anti-inflammatory effects which might contribute to their beneficial effects. Metabolism of omega-6 PUFAs generally results in proinflammatory mediators. Several specific studies have shown such PUFAs to be beneficial for supporting liver function. For example, one mouse study showed that those receiving a high fish oil diet for 8 weeks had beneficial effects on hepatic insulin resistance, lipogenesis, and beta-oxidation and prevented hepatic tissue from liver damage and NAFLD (Bargut et al. 2014). A limited number of preliminary clinical trials have suggested that treatment of patients with nonalcoholic fatty liver disease with PUFAs helps improve liver function and outcomes, but larger trials will be necessary (Bouzianas et al. 2013).

Perhaps the most relevant trial was performed on 66 patients with end-stage liver disease or hepatocellular carcinoma who underwent liver transplantation and administration of isocaloric and isonitrogenous parenteral nutrition for 7 days following surgery (Zhu et al. 2012). One group received standard parenteral nutrition while the other group received parenteral nutrition with PUFAs replacing part of the standard lipid emulsion. The results showed that those patients receiving the PUFA nutrition had reduced injury to their hepatic cells. In addition, the PUFA-treated group had slightly reduced hospital stays, reduced complications, and improved 1-year survival. The authors concluded that parenteral nutrition with PUFA may be of benefit in patients receiving liver transplantation.

Alpha-lipoic acid is generally involved in energy metabolism but also acts as a powerful antioxidant, which may help protect hepatocytes from oxidative damage associated with various drugs, toxins, or pathophysiological processes. Several studies have identified specific circumstances in which lipoic acid may help support hepatocytes.

A mouse study of lipopolysaccharide (LPS)/d-galactosamine (d-GalN)-induced fulminant hepatic failure showed that those pretreated with lipoic acid had marked reductions in oxidative damage markers such as iNOS, COX-2, TNF-α, NF-κB, IL-1β, and IL-6 levels (Xia et al. 2014). Lipoic acid also improved apoptotic features in hepatocytes. Taken together, the results indicated that LA plays an important role on LPS/d-GalN-induced fulminant hepatic failure through its antioxidant, anti-inflammatory, and antiapoptotic activities. In both mouse and in vitro cell studies (Yang et al. 2014), alpha-lipoic acid was found to increase nuclear NF-E2-related factor 2 levels and reduce intrahepatic and serum triglyceride content. The studies suggest that alpha-lipoic acid protects against hepatic steatosis by modulating the transcription factors sterol regulatory element-binding protein-1, forkhead box O1, and NF-E2-related factor 2. One study of rats given liver toxic doses of acetaminophen suggested that lipoic acid may help protect the liver in a manner similar to n-acetyl cysteine (Elshazly et al. 2014).

NAC is a strong antioxidant and has been used in one particular situation regarding the liver, acetaminophen overdose, or toxicity. The primary mechanism is to help prevent the depletion of antioxidants such as glutathione in the liver in the face of large quantities of acetaminophen. However, it is possible that the antioxidant properties of NAC might be useful in the setting of liver transplantation. For example, a study of rats used for partial liver transplantation showed that when the liver was treated in cold storage with NAC, that NAC treatment resulted in improved microcirculation and functional quality of the partial liver graft. The authors suggest that the use of NAC helped increase antioxidant capacity in the liver graft and also reduced lipid peroxidation.

However, a study of 88 patients undergoing liver resection did not show any significant improvements in patients who had received perioperative NAC. It should be noted that the NAC group did have lower rates of liver failure, but this did not achieve significance (Robinson et al. 2013).

S-adenosyl-l-methionine is an important physiological molecule that participates in multiple cellular reactions. Its primary roles include being a precursor for the synthesis of glutathione and functioning as a principle methyl donor of nucleic acids, phospholipids, histones, biogenic amines, and proteins. SAMe synthesis is typically depressed in chronic liver disease so supplementation has been considered a potentially important therapeutic intervention. However, there have been no conclusive trials or adequate data to support or refute the use of SAMe in patients with chronic liver disease (Anstee and Day 2012). Several examples more specifically related to liver transplantation are described below.

A preliminary study of 81 HCC patients with chronic HBV infection, undergoing partial hepatectomy with inflow occlusion, were treated with SAMe either two hours before surgery or 6 h after surgery and compared to a control group that did not receive SAMe (Liu et al. 2014). In this study, the preoperative administration of SAMe significantly reduced the plasma levels of alanine transaminase (ALT), aspartate transferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL) as compared to the other two groups. Administration of SAMe postoperatively resulted in significant reductions in TBIL and DBIL compared to controls. Measures of IL-6 and TNF-α were significantly different between the preoperatively treated group and the other groups. Preoperative administration of SAMe reduced the risk of complications and the hospital stay after surgery.

A rat study evaluated the effect of 5′-methylthioadenosine (MTA), which is a nucleoside generated from S-adenosylmethionine, during liver transplantation. The results showed that pretreatment with MTA significantly improved liver function and reduced hepatic ischemia-reperfusion injury by downregulating TNF-α level and suppressing the postsurgical inflammatory response (Tang et al. 2014). Administration of MTA was also associated with the inhibition of IκBα degradation, NF-κB transcriptional activity, and the activation of MAPK signal. Thus, the beneficial effect of MTA in liver transplantation appeared to be mediated by inhibiting the activation of the NF-κB and MAPK signal pathways. However, another study of rats with liver steatosis found no beneficial effect of S-adenosylmethionine on ischemia-reperfusion injury during liver transplantation (Pantoflicek et al. 2012).

Taurine derivatives have been evaluated in liver transplant patients. A pilot study of 10 cirrhotic patients awaiting liver transplantation were given tauroursodeoxycholic acid until liver transplantation while evaluating a variety of liver function parameters (Caglieris et al. 2000). For example, liver cholestasis and cytolysis parameters decreased along with serum gamma-glutamyl transpeptidase at the 4th month of therapy compared to pretreatment values and compared to a group of untreated historical controls.

An optimal vitamin D status may benefit liver transplantation (LT) patients by helping them to maintain adequate muscle and bone mass and reduced inflammatory effects. One study evaluated 25(OH)D in banked specimens from 154 human immunodeficiency virus-positive patients with advanced liver disease who were liver transplant candidates/recipients (Branch et al. 2014). The study showed that 71 % of patients had vitamin D deficiency prior to transplantation, and this improved to approximately 40 % of patients posttransplant. The authors also reported that none of the 17 academic medical centers involved in this study routinely recommended vitamin D supplements prior to transplant, and only 4/17 recommended vitamin D supplementation after surgery. However, this study did not evaluate whether the deficiency in vitamin D levels was associated with poorer outcome posttreatment.

Another study evaluated 133 patients who received a liver transplant (Bitetto et al. 2010). Overall, these patients were found to have a median 25-hydroxyvitamin D level that was below normal, and 79 of these patients were treated with supplemental oral vitamin D. The authors found that in the 2 months following transplant, lower pretransplant serum 25-hydroxyvitamin D levels were associated with an increased risk of moderate-to-severe acute rejection episodes. In addition, oral vitamin D supplementation (within the first month after the transplant) was associated with a reduced incidence of acute rejection episodes.