Perioperative Supplementation

Ypera ® Ultra Regeneration Gel can be beneficial also for Pre- and Postoperative Micronutrient Supplementation and Optimization.


Over the last decades, modern surgery has made not only tremendous progress in the Field of applied surgical techniques conducted in specialized centers, but also in intensive care therapy. More and more significant operations in a patient group that is getting more and more ill and older have become possible. The price to be paid is that more complicated progressions of diseases occur post-operatively, which implies the necessity of more extended stays in intensive care units (ICUs). Surgery puts its emphasis on optimizing the general condition and the fitness of the patient aiming that the cure goals do not exclude the multimorbid patients.

Literature shows that protocols or programs under the terms “fast track surgery” or accelerated rehabilitation programs” can be found. (1 – 7)

These programs can be complemented by the modern supplementation of performance-optimizing and oxidative stress-reducing substances, because the pathophysiology of the most known problems occurring postoperatively, such as systemic inflammable response syndrome, sepsis, etc., are associated with these mechanisms. (8 – 18)

Oxidative Stress in Surgical Interventions

Artificial respiration leads to the systematic formation of radicals. The inset of narcosis effects also increases the oxidative potential.

In general, four classes of natural compounds are oxidized:

  1. Nucleic Acids – Damage of genetic material
  2. Carbohydrates – Disturbance of the energy metabolism
  3. Lipids – Energy metabolism, membrane damage
  4. Proteins – Disturbance of the transport function, the form of storage, the underlying physiological reactions, disturbance of collagen synthesis, fibrosis, hormones, eg.

Oxidative stress with its main effect in endothelial cells and granulocytes seems responsible for the occurrence of SIRS (systemic inflammatory response syndrome) and the induction of postoperative cascades of complications with all the clinical appearances.

Pathophysiology in Surgical Interventions

During surgical interventions, it is possible that through different performed maneuvers oxygen deficiency of the tissue (ischemia) occurs. As blood circulation is restored, effects like reperfusion and vasodilatation take account.

Through oxygen deficiency, a multitude of free radicals and RONS generate, if antioxidative repairment fails.

During reperfusion lipid mediators, polypeptides, hormones, and immune complexes increase, which results in dysfunction of endothelial cells and the inflow of monocytes, neutrophils, and macrophages within the alveolar-capillary membrane. The resulting chain reaction also leads to an increase of RONS, which interacts with alveolar cells or generate repaired collagen. Under normal conditions, endogenous antioxidative mechanisms or anti-trypsin- proteins compensate for these consequences.

Through hypoperfusion and reperfusion, these endogenous defense mechanisms get insufficient, and the increase of RONS leads to reoxygenation injuries in cells and dysfunction of organs.

As a pathological model of ischemia or reperfusion injuries during thoracic surgical procedures under single lung ventilation are described in the following. Similar procedures can also be observed in other big visceral surgical interventions (cardiac surgery, liver surgery, vascular surgery) under given conditions of ischemia.

Pathophysiology of Pulmonary Hypertension caused by Oxidative Stress

The reperfusion leads to increased production of superoxide anion radical through NADPH oxidase in the smooth muscle cells of the pulmonary vessels. This cascade enhances the vasoconstriction of pulmonary vessels that is indicated by 5-hydroxytryptamine. The resulting RONS lead additionally to the production of endothelin-1 as a potent vasoconstrictor. These reactions result in pulmonary hypertension with all its clinical appearances such as the steady increase of the vascular resistance and the increase of blood pressure in the pulmonary circulation, often connected to a followed right- heart failure.

Pathophysiology of Cardiac Arrhythmias caused by Oxidative Stress

Hydroxyl radicals and nitrogen monoxide radicals that form to peroxynitrite are primary factors for structural and biochemical disturbances in the cardiomyocytes because of the formation of protein nitrotyrosine, nitro-arginine, etc. Nitro-arginine acts as a potent inhibitor of eNOS.

The influx of inflammatory cells through oxidative stress fasters the arrhythmogenic effect; in addition, free radicals cause cardiac arrhythmias through the inhibition of sarcolemmal Na/K-ATPase activity. These changes influence the energy status and the electrophysiological and mechanical properties of the heart cells.

Pathophysiology of Re-expansion Damages of the Lung

The arising complications and damages can be observed in all surgical interventions. (general surgery, accident surgery, orthopedic surgery, cancer surgery, vascular surgery, cardiac surgery, thoracic surgery, plastic surgery).

Of course, burdens and damages of more significant and more severe surgical interventions can be seen to a greater extent (i.e., patients with abdominal or thoracic surgical cancer operations) and are therefore especially relevant for the application of new therapies as an exemplary group.

Pre-Operative Burden

Targeted preparation of the patients and a good plan of an elective surgical intervention can improve the physical abilities of the patient and the probability of complications can be reduced. For many of these patients time plays an important role because development programs over weeks or months are not possible from the point of view of doctors as well as from that of patients.

Programs such as nicotine and alcohol abstinence, fitness programs and the implementation of healthy nutritional strategies can be supplemented by appropriate supplementation of performance-optimizing and oxidative stress-reducing substances, as these are associated with the pathophysiology of the most well-known postoperative problems.

Therefore, nutritional programs use substances that improve physical performance and reduce oxidative stress within a short time.

Important characteristics concerning the improvement of the general condition are:

  • Increased ATP production
  • Optimization of the myocardial protein synthesis
  • Optimization of muscle protein synthesis
  • Reduction of RONS

Consequences are:

  • Faster access to urgently or vitally needed operations
  • Optimized operating procedures
  • Reduced occurrence of complications during and after surgery
  • Streamlined and faster healing process

Hospitalization and intensive care stay can be significantly reduced, leading to an improvement in the micro and macroeconomic situation in the healthcare sector.

The preoperative optimization is one of the most critical preconditions in reducing complications during and after surgical interventions. (19 – 23)

Burden through Surgical Interventions

The underlying biochemical effects in all surgeries depend on two main results – the “Oxidative burst” and the “Decrease of ATP Synthesis.”

Health effects:

  • Intraoperative ischemia/reperfusion induced cell-killing
  • Systemic Inflammatory Response Syndrome (SIRS)
  • Reduced myocardial oxygenation
  • Reduced muscular protein synthesis

Oxidative Burst

The oxidative onset is based on damage during ischemia and reperfusion as well as mitochondrial dysfunction. The reduction of mitochondrial oxidation capacity and the formation of free radicals and their intermediates (RONS) are additional symptoms of this process.

Decrease of ATP Synthesis

The decrease in ATP synthesis has a high reliance on anaerobic metabolism. An early lactate formation leads to a restriction on exercise. The effect coming out of this is that training is limited, and necessary activities for recovery cannot be carried out.

Low peak work rate and low peak oxygen consumption lead to a severe restriction of the patient.

Lower activities of mitochondrial enzymes are also accessory symptoms of the decrease of the ATP Synthesis.

Especially lung resection will lead to a decrease in lung function. However, the patients requiring lung cancer surgery suffer more and more from concomitant pulmonary and circulatory disorders, usually caused by cigarette smoke. Because their resection tolerance is limited, preoperative assessment of these patients includes spiroergometry and postoperative lung function assessment based on radioisotopic ventilation-perfusion studies. Since resection itself and functional adaptation during the postoperative period put a massive strain on both circulatory and respiratory reserves, the determination of preoperative resilience (VO2max) has proven to be the most sensitive predictor of post-resection morbidity and mortality. (2124)

There is increasing evidence that 2-5% of the total electron flow through the cytochrome chain during intense training or surgical trauma leads to the formation of superoxide anion radicals. (25, 26) This can significantly increase the formation of reactive oxygen and nitrogen species (RONS) in various tissues such as muscle fibers, endothelial, lung, heart, or liver cells. (20)

Oxidative stress injury resulting from intra-operative manipulation, ischemia, or non-ventilation eventually causes hypoxic cellular damage (20). Also, decreased oxygenation (decreased blood supply) occurs in hypoxic vasoconstriction, while subsequent re-expansion, along with reentry of airway oxygen, induces reactive pulmonary vasodilation during reperfusion of the lung. Ischemia-reperfusion sequence is associated with the formation of oxygen free radicals. They interact with cellular structural molecules provoking dysfunction, mostly of endothelial cells.

Considering these pathophysiological pathways, complications after major surgery, especially lung surgery, may be related to factors in the surgical stress response with endocrine-metabolic and inflammatory changes. (2027)

Metabolic Response to Surgery

Protein hyper catabolism:

  • Unavoidable consequence of injury and cause of morbidity and mortality. More severe SIRS in patients with protein malnutrition
  • Immune nutrition can be used to modulate the response to surgical stress five days before surgery. 1000 ml/day reduce the postoperative complications
  • Systematic review of perioperative nutritional supplementation: 10 studies supporting the study of nutritional support after duodeno-pancreatectomy, postoperative enteral nutrition seems to be beneficial
  • Preoperative carbohydrate exposure significantly reduces postoperative hospitalization. tends to have an earlier bowel function compared to fasting or extra water
  • VO2max is essential to describe exercise capacity
  • Postoperative QCL depends on cigarette smoke and nutrition

However, data from studies support the hypothesis that a significant reduction in oxidative stress and an improvement in preoperative resilience with its complex pathophysiological signaling pathways correlate with clinical outcome i.e., Reduction of the intensive care unit, the hospital stay and last but not least the total costs.

Postoperative Burden

The healing process, rehabilitation, and recovery after major surgery also depend on the stresses that occur after such operations. On the one hand, when the body is burdened with the removal of damaged tissue (formation of toxic substances), the organism requires an increased energy supply for the creation of new cells. The approaches to ensure this correspond to the preoperative pressure.

Integrated Overview and Conclusions

Recent findings in perioperative pathophysiology have shown that multimodal concepts are needed to reduce postoperative morbidity and mortality. (22)

These efforts are an extension of the conventional “clinical pathways” that focus on the preoperative optimization of organ dysfunction, the reversal of malnutrition, pain physiology and treatment, anesthesia, surgical technique, and early mobilization and rehabilitation, including forced postoperative nutrition focus. The terminology for such programs included terms such as “fast track” or “accelerated recovery programs” with the characteristic feature of shortening hospitalization with lower morbidity and lower overall costs.

These programs are based on a variety of measures to increase preoperative resilience. They reduce stress-related organ dysfunction and the associated morbidity, which otherwise lead to later hospitalization and complication management.

Besides, the results of preoperative micronutrient optimization using suitable substances lead to the hypothesis that perioperative use in parenteral and oral preparations may enhance these effects.

Dietary supplement based on:

  • Energy generation (ATP) in the cells
  • Optimization of oxygen utilization in human tissues
  • High antioxidant potential
  • Build up and reduction of nonessential amino acids
  • Reduction of toxic substances

are qualified to be the right approach for patients.

Perioperative Supplementation with Ypera®

Ypera® Ultra Regeneration Gel can be beneficial also for Pre- and Postoperative Micronutrient Supplementation and Optimization.

Ypera®’s QoL Enhancer™ ingredients are able to assist with the:

Preventative and concomitant decrease of metabolic changes (stress reactions after physical trauma caused by emotional or physical strain) through the enhancement of the body’s performance and the reduction of oxidative stress.

  • Before surgical procedures, especially in instances of poor health
  • After surgery, accidents, and serious illnesses
  • During and after the rehabilitation period (for example: burnout)

Only to be used under the supervision of a doctor! 

Ypera® is a Dietary Food Supplement designed to enhance your Quality of Life. Ypera® is not meant to prevent, treat, or cure any disease, and it is Not a Medical Drug.

Consult your physician if you are suffering from allergies, are undergoing medical treatment, or are pregnant or nursing before taking Ypera®. Stop using Ypera® if you notice any side effects.


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