Surgery - Preparation and Recovery
Modulating immune function to achieve a proper balance of host defenses against infection, while minimizing exaggerated inflammatory responses to surgery, is an important goal of integrative interventions in the perioperative and wound healing settings. Adequate protein intake prior to surgery provides the soon-to-be-healing body with building blocks of new tissue. Optimal micro- and macronutrient intake can be achieved with a reasonable program of supplementation and good dietary habits in the weeks prior to surgery.
The advantages of drinking immunonutrition shakes before surgery have been discussed in the preoperative section of this protocol. Patients may also benefit from drinking immunonutrition shakes after surgery. Immunonutrition formulas helped patients get fewer infections and have shorter stays in intensive care and fewer overall hospital days (Xu, Sun 2018; Bharadwaj 2016; Palma-Milla 2018; Scislo 2018). Immunonutrition shakes may also improve wound healing (Celik 2009; Lorenz 2015).
Although many different mixtures of nutrients have been used in immunonutrition formulas, several main components appear to provide maximum benefits. Most immunonutrition preparations contain healthy fats such as omega-3 fatty acids, proteins and their amino acid building blocks, and a variety of vitamins and minerals (Chow 2014; Bharadwaj 2016).
Most effective immunonutrient supplements contain substantial quantities of omega-3 fatty acids. Omega-3 fatty acids are polyunsaturated fatty acids, largely derived from fish oils. These fatty acids can shift the production of cytokines away from those that stimulate inflammation (Ventro 2017; Calder 2017). They also make cell and mitochondrial membranes more resistant to oxidative stress (Calder 2017), which reduces tissue damage and prevents amplification of the inflammatory response. A diet enriched with fish oil has been shown to help treat pressure ulcers (Theilla 2012).
Immunonutrition preparations also often contain arginine and glutamine (Bharadwaj 2016; Chow 2014). These amino acids are described as conditionally essential, which means that under certain stressful conditions (including trauma and surgery), the body cannot synthesize them in normal amounts; it must therefore rely on supplemental sources (Nieves 2002; Albaugh 2017; Hall 1996).
The amino acid arginine provides a substrate for nitric oxide production, which enhances blood flow by relaxing blood vessels and promotes the synthesis of collagen used in wound healing (Chow 2014). It also stimulates and activates immune system cells and helps T cells proliferate (Bharadwaj 2016). Trauma, surgery, and oxidative stress increase the levels or activity of the enzyme arginase, which reduces arginine levels (Engelen 2017; Ochoa 2000; Chandra 2012). Arginine supplementation may enhance wound healing, particularly in combination with omega-3 fatty acids (Alexander 2014) and may help heal pressure ulcers (Liu, Shen 2017; Cereda 2015).
The amino acid glutamine is a major component of proteins produced during clotting (Weisel 2005) and a source of energy for immune cells (Chow 2014). It can also help control the effects of inflammation, primarily by increasing levels of heat shock proteins, which protect cells from stress (Chow 2014; Hartmann 2017; Jordan 2016).
Vitamin C, which is included in some immunonutrition preparations, is an antioxidant required for the synthesis of certain proteins, making it indispensable in wound and fracture healing. Several studies showed that a better vitamin C status may protect against fractures (Aghajanian 2015; Moores 2013). In patients with wrist fractures, vitamin C supplementation (500 mg per day) was helpful in relieving pain (Zollinger 2007).
Vitamin C may be especially helpful for patients undergoing heart surgery. In one randomized study, patients undergoing heart surgery were treated with either a placebo or vitamin C (2 grams intravenously just before surgery and 1 gram per day orally for four days after surgery). The vitamin C group had shorter hospital stays and shorter intubation times (Sadeghpour 2015).
After coronary artery bypass surgery, many patients suffer from abnormalities in their heart rhythm called atrial fibrillation that can be dangerous. Inflammation and oxidative damage is one contributing factor (Boos 2006). Fortunately, vitamin C may help reduces markers of oxidative stress after coronary artery bypass surgery (Safaei 2017).
Three meta-analyses have been published recently that combine data from multiple clinical trials testing the effects of vitamin C on the incidence of atrial fibrillation after coronary artery bypass surgery (Baker 2016; Hu 2017; Polymeropoulos 2016). In most of the trials, patients were treated with 2 grams of vitamin C within 24 hours before surgery and 1 gram per day for several days after surgery. All three meta-analyses found that vitamin C supplementation significantly reduced the incidence of atrial fibrillation.
Vitamin E is a potent antioxidant and fat-soluble vitamin found in large amounts in the skin, where it may improve wound healing and scar appearance (Hobson 2016; Zampieri 2010). By scavenging reactive oxygen species, vitamin E can reduce tissue damage caused by free radicals, thereby reducing surgically induced inflammation (Souyoul 2018). Vitamin E levels are depleted during surgical procedures, especially those that require use of a heart-lung machine (Schindler 2003; Valle-Giner 2007).
A 2017 study found that vitamin E applied under the skin of the surgical incision site helped reduce the rate of surgical site infections among patients having surgery for colorectal cancer, and decreased pain after surgery (Alias 2017). Vitamin E supplementation may also help bones heal. In animal models, supplements containing vitamin E promoted fracture healing (Shen 2017; Ibrahim 2014). In humans, vitamin E (1,000 IU per day) may help repair bone damage that occurs after radiation treatment (Delanian 2005; Aggarwal 2017).
Vitamin D is critical for bone health, including bone formation and maintenance, and may be particularly important for patients undergoing orthopedic surgery (Turner 2012; Gennari 2001; Mabey 2016; Rodriguez 2013). An analysis of people scheduled for orthopedic surgery found that low levels of vitamin D affected about 40% of patients (Bogunovic 2010). Vitamin D supplementation was found to significantly improve functional recovery among patients undergoing knee replacement (Maniar 2016), and vitamin D supplementation improved the quality of life among patients recovering from surgery to repair a hip fracture (Sprague, Slobogean 2017). A study on elderly patients who underwent surgery for hip fracture found that only about 39% of the patients took vitamin D supplements consistently (Sprague, Madden 2017).
Omega-3 Fatty Acids
Omega-3 fatty acids have already been discussed as a critical component of immunonutrition formulas, but omega-3 fatty acids and fish oils have also been studied outside of that context. Supplementation with omega-3 fatty acid rich fish oil may reduce the risk of infection and other complications, shorten hospital stays, and improve nutritional status and liver and pancreatic function in postoperative patients (Calder 2018; Heller 2004; Ma 2016). A meta-analysis and review of evidence on patients who underwent surgery for gastrointestinal cancers reported that omega-3 fatty acids improved nutritional status, improved immune function, and decreased inflammation (Yu 2017). In patients undergoing heart surgery, supplementation with omega-3 fatty acids (2 to 10 grams per day) decreased the length of hospitalization and risk of certain heart rhythm problems after surgery (Langlois 2017). Moreover, omega-3 fatty acids may reduce the risk of death after abdominal surgery and improve recovery (Zhang 2017; Tsekos 2004).
Fish oil supplements may reduce the exaggerated inflammatory response that accompanies surgery (Ma 2015; Aiko 2005; Wang 2016). Among 861 patients recovering from kidney transplant, those with low levels of omega-3 fatty acids in their plasma had the highest levels of proinflammatory cytokines (Eide 2017).
Coenzyme Q10 (CoQ10) is an antioxidant molecule intimately involved in energy production in cells (Saini 2011; Deichmann 2010). CoQ10 levels plummet markedly after surgery, presumably because of rapid consumption by oxidant species (Liu, Cheng 2017; Pechan 2004). In a randomized placebo-controlled clinical trial, a dose of 300 mg per day of CoQ10 improved antioxidant capacity and reduced inflammation in patients undergoing surgery for liver cancer (Liu 2016). Supplementation with CoQ10 has been associated with a significant decrease in the proinflammatory cytokines tumor necrosis factor-alpha, C-reactive protein, and interleukin-6 (Zhai 2017; Fan, Feng 2017).
Supplementation with CoQ10 has been shown to reduce mortality and improve exercise capacity in people with heart failure (Lei 2017; DiNicolantonio 2015; Sole 2002). Poor cardiac output results in poor blood flow to other organs, can delay healing, and may set the stage for other complications. Preoperative treatment with CoQ10 can support cardiac muscle function and protect against complications (Makhija 2008; Keith 2005; de Frutos 2015).
Zinc is a mineral that functions as an important cofactor for several enzymes involved in wound healing (Lin 2017). Adequate zinc is critical for healthy skin in general (Rostan 2002). Even those with only a mild deficiency may have poor wound healing and roughened skin (Lin 2017; Lansdown 2007; Kogan 2017). Researchers studying wound healing have found evidence that zinc is involved in every step of the process, including clotting, immune response, and the regrowth of tissue (Lin 2017; Taylor 2016).
The topical application of zinc may be beneficial to surgery patients or other patients with healing wounds (Lin 2017; Attia 2014) and venous leg ulcers (O'Connor 2014; Moreno-Eutimio 2018). Zinc supplementation improved the antioxidant status of patients recovering from burns (Berger 2007), possibly by upregulating a protein called metallothionein (Lin 2017; Rostan 2002). Animal studies showed that wound healing increases the need for zinc in the wound tissue, especially in the first few days, and zinc-dependent enzymes are critical for cell proliferation and wound healing (Kaplan 2004). Zinc administration locally, inside the bone, also improved fracture healing in rats (Krell 2017).
Melatonin is a hormone primarily produced in the pineal gland that affects a variety of brain functions related to sleep and wakefulness (Macchi 2004; Brown 1994). Melatonin production can be perturbed by surgery and anesthesia (Yasar 2017; Karkela 2002; Hanania 2002). It is thought that these disturbances may be correlated with certain neuropsychological changes, such as anxiety or depression, after major surgeries (Yin 2007).
Melatonin supplementation may be beneficial to surgery patients. Patients who took melatonin (1 mg per day) the night before hip surgery and for five days afterwards had better cognitive function after surgery (Fan, Yuan 2017). Similarly, patients who took melatonin the night before bariatric surgery and two hours before the procedure had better recovery, including less pain and better sleep (Ivry 2017).
During surgery, tissues are first denied sufficient oxygen when blood flow is restricted to the target area and then oxygen levels rapidly increase when blood flow is restored. This can result in oxidative stress and tissue damage. Melatonin is a free radical scavenger, which neutralizes free radicals that could otherwise damage tissues (Esteban-Zubero 2016; Mortezaee 2018). Melatonin can also reduce levels of the proinflammatory cytokine tumor necrosis factor-alpha (Esteban-Zubero 2016). Melatonin (10 to 20 mg per day) may decrease complications due to oxidative damage in patients undergoing heart surgery (Dwaich 2016; Gogenur 2014).
Curcumin, a major component of the spice turmeric, is a potent inhibitor of nuclear factor-kappa B, which plays a central role in the inflammatory response (Seo 2018; Shah 2017). There has been tremendous interest in inhibiting nuclear factor-kappa B to decrease the overactive inflammatory reactions in sepsis, cancer, and autoimmune diseases (Maheshwari 2006; Park 2016; Abraham 2003). Curcumin is also a powerful antioxidant (Hewlings 2017). Supplementation with curcumin (1‒1.5 grams daily) has been shown to improve markers of oxidative stress in patients with various conditions, including type 2 diabetes, osteoarthritis, and metabolic syndrome (Panahi 2017; Panahi 2016; Panahi 2015).
Alpha-lipoic acid is a sulfur-containing antioxidant found in spinach, broccoli, and tomatoes (Tibullo 2017; Gomes 2014; Hodges 2015). Lipoic acid can have two chemical forms, R and S. The R form is the natural form and is more readily absorbed by the body (Hermann 2014). Lipoic acid protects against oxidative stress and is essential for proper utilization of glucose in cells (Ambrosi 2018; Poh 2009).
In humans, alpha-lipoic acid may help combat free radical damage caused by high tissue concentrations of oxygen (Alleva 2005; Ambrosi 2018). In one study, 24 patients undergoing liver surgery were treated with either 600 mg alpha-lipoic acid or placebo 15 minutes before surgery began (Dunschede 2006). After surgery, blood tests for liver damage were significantly better in the alpha-lipoic acid group than in the placebo group.
Another study enrolled patients who were undergoing surgery for a simultaneous kidney and pancreas transplant (Ambrosi 2016). Surgery patients and organ donors were either untreated or treated with 600 mg alpha-lipoic acid just before surgery. After surgery, markers of inflammation and indicators of kidney damage were both decreased in the alpha-lipoic acid-treated patients.
Propolis, a resin produced by honey bees from a variety of plant sources, has antimicrobial properties that may help heal wounds (Oryan 2018). An ointment containing propolis may help heal wounds in patients with diabetes (Afkhamizadeh 2017; Henshaw 2014). Mice supplemented orally with a propolis extract had lower levels of inflammatory cytokines and their surgical wounds closed faster (Correa 2017). Another study testing a propolis cream found similarly enhanced wound healing in rats (Iyyam Pillai 2010).
Probiotics are live beneficial microorganisms that improve health when used as a supplement. They keep “bad” bacteria in check. Probiotics may be particularly helpful for patients undergoing colorectal and other abdominal surgeries (Komatsu 2017; Liu, Yan 2017). In an analysis that combined data from 28 randomized clinical trials, patients undergoing gastrointestinal surgery were significantly less likely to have infections after surgery if they were taking probiotic supplements (Yang 2017). The data are particularly strong for patients taking probiotic supplements containing multiple strains (Liu, Yan 2017), but studies have not yet determined the best combinations.
N-acetyl cysteine (NAC) is a precursor of the amino acid cysteine (Sansone 2011) and the antioxidant glutathione (Ramachandran 2018; Schmitt 2015). NAC is used to prevent liver damage in patients who overdose on acetaminophen (Ramachandran 2018). NAC may help protect liver tissue from the damaging effects of reactive oxygen species during and after surgery. In one study, patients treated with NAC were less likely to have liver damage following liver surgery compared with patients who received a placebo (Donadon 2016). Another study found that patients who underwent liver surgery were less likely to have mild or severe liver failure than control patients if they received 10 grams of NAC per day intravenously, starting during surgery and continuing for three days afterwards, although the difference was not significant (Robinson 2013).
Similarly, one study found that NAC, administered for three days before surgery, may help protect the lung tissue in patients with chronic obstructive pulmonary disease undergoing coronary artery surgery (Erdil 2016). In another study conducted in 70 similar patients, half of them were treated with NAC (900 mg daily) for seven days before surgery and half were untreated. Several blood tests for kidney and liver function were significantly improved in the group receiving NAC compared with the control group (Onk 2018).
Bromelain is an extract from pineapple that has anti-inflammatory properties (Hale 2010; Muhammad 2017). For instance, as shown in an animal model, bromelain can inhibit signaling through tumor necrosis factor-alpha, a pro-inflammatory cytokine (Zhou 2017). Bromelain can also interact with molecules in the pain pathway (Pavan 2012). Bromelain's effects on postoperative pain have been well studied among patients undergoing wisdom tooth extraction. Although not all studies had significant results, patients treated with bromelain typically had less pain and swelling than patients treated with a control (Bormann 2016; Ghensi 2017; Majid 2014).
Beta-hydroxy beta-methylbutyrate, or HMB, is a metabolite of the amino acid leucine that can help prevent muscle wasting (Holecek 2017). Several studies have suggested that 1.5‒3 grams per day of HMB can help maintain muscle mass in patients with conditions that restrict their activity, such as those recovering from hip fractures (Malafarina 2017) and those with lung disease (Olveira 2016).
HMB may also prevent muscle wasting in patients undergoing surgery. In one study, 23 patients undergoing total knee replacement took a supplement containing HMG, arginine, and glutamine or a control for five days before and 28 days after surgery (Nishizaki 2015). Patients in the control group had a significant loss of muscle strength after surgery, but patients in the supplemented group did not.
Aloe vera, a plant that grows naturally in tropical climates and is commonly kept as a house plant, contains several bioactive phytochemicals. This plant has traditionally been used to help alleviate various skin conditions, and aloe is a common ingredient in over-the-counter skin medications and lotions (Akaberi 2016; Pereira 2016). Aloe has been found to promote wound healing by reducing inflammation and boosting collagen synthesis and blood supply (Pereira 2016).
One study specifically evaluated the effect of an aloe vera gel on surgical wounds, in this case from Cesarean sections. In 45 women, wounds were dressed with an aloe vera gel. A standard dressing was used for a control group of 45 women. After 24 hours, wound healing was significantly improved in the aloe vera group compared with the control group (Molazem 2014).
Pycnogenol is an extract from Maritime pine bark that is rich in free radical-scavenging, anti-inflammatory polyphenolic compounds (Deger 2013; Grether-Beck 2016). A growing body of evidence suggests that pycnogenol may have positive effects on skin health, improving elasticity and hydration and protecting against damage related to sun exposure (Grether-Beck 2016). In a randomized clinical trial, 30 patients with venous ulcers were treated with surgery followed by 50 mg of pycnogenol three times daily or a flavonoid combination previously shown to enhance vascular healing for 90 days. Pycnogenol was found to be as effective as the flavonoid combination at promoting healing of surgically-treated venous ulcers (Toledo 2017). Findings from another trial suggest the use of both topical and oral pycnogenol may be more effective than oral pycnogenol alone for improving healing of venous ulcers (Raffetto 2014). Another clinical trial found that oral (systemic) and topical (local) pycnogenol preparations, alone and in combination, led to higher rates of complete healing of diabetic ulcers after six weeks of use compared with standard medications (Belcaro 2006).
In a study in rats subjected to experimental injury, the use of topical 1%, 2%, and 5% pycnogenol solutions shortened wound healing time and reduced scar size compared with pycnogenol-free solution, and the benefits were amplified as pycnogenol concentration increased (Blazso 2004). Abdominal injections of a pycnogenol solution for ten days after abdominal surgery was found to reduce adhesions better than abdominal saline injections in rats that had undergone abdominal surgery (Sahbaz 2015). Another study in rats showed that a topical pycnogenol solution reduced tissue oxidative stress and improved healing of incision wounds, and a solution made with an extract from the bark of another type of pine tree had even stronger effects (Cetin 2013).
Diabetes is well known to impair skin healing, and one animal study showed that pycnogenol may counter this problem. In the study, topical treatment with pycnogenol powder reduced the size of wounds compared with no treatment three weeks after surgical removal of small areas of skin in diabetic rats (Dogan 2017). Findings from another study in rats suggest that oral pycnogenol may reverse the negative impact of prior radiation therapy on post-surgical healing time (Deger 2013).
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This information (and any accompanying material) is not intended to replace the attention or advice of a physician or other qualified health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a physician or other qualified health care professional. Pregnant women in particular should seek the advice of a physician before using any protocol listed on this website. The protocols described on this website are for adults only, unless otherwise specified. Product labels may contain important safety information and the most recent product information provided by the product manufacturers should be carefully reviewed prior to use to verify the dose, administration, and contraindications. National, state, and local laws may vary regarding the use and application of many of the treatments discussed. The reader assumes the risk of any injuries. The authors and publishers, their affiliates and assigns are not liable for any injury and/or damage to persons arising from this protocol and expressly disclaim responsibility for any adverse effects resulting from the use of the information contained herein.
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