Diet Rich in N-3 Polyunsaturated Fatty Acids in Renal Transplant Recipients
Condition: Kidney Transplantation
Study type: Interventional
Phase: Phase 4

Summary: 
      n-3 Polyunsaturated fatty acids (PUFAs) supplementation reduces systemic inflammation and
      improves renal and cardiovascular prognosis in kidney transplant recipients. A good patient
      compliance is often difficult to obtain because bad tasting fish oils are used as n-3 PUFA
      source. Therefore, we explored whether n-3 beneficial effects can be obtained by
      administering a diet based on n-3 rich foods.
    

Detailed description: 
      An emerging concept in clinical nutrition is that dietary interventions may improve the
      course of systemic inflammatory disorders like rheumatoid arthritis and psoriasis. Most of
      this effect depends on the ability of polyunsaturated fatty acids (PUFAs) to modulate immune
      and inflammatory responses. Two main families of PUFAs exist in human tissues: n-3 PUFAs that
      have a marked anti-inflammatory activity and n-6 PUFAs that, conversely, promote
      inflammation. Multiple mechanisms account for the modulation of the inflammatory response by
      PUFAs. Recent lipidemic studies have added new mediators like lipoxins to the list of PUFA
      metabolites controlling inflammation that classically included only pro-inflammatory or
      anti-inflammatory prostaglandins like PGE2 and PGE3, respectively. The concerted activity of
      these mediators may determine a decreased recruitment of inflammatory cells in target
      tissues, with a lower release of pro-inflammatory cytokines like Interleukin-6 (IL-6) and
      necrosis tumor factor-α (TNF), and their higher apoptosis rate.

      n-3 PUFAs include α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic
      acid (DHA), whereas linoleic acid (LA) and arachidonic acid (AA) are the main n-6 PUFAs. ALA
      and LA are both essential fatty acids because they cannot be synthetized in the human body
      and have to be assumed with the diet. They are the precursors of downstream immunomodulatory
      long-chain fatty acids: LA is converted to AA that has marked a pro-inflammatory activity and
      is further transformed in pro-inflammatory eicosanoids (PGE2) and leukotrienes. On the
      contrary, ALA is converted to EPA and DHA, the precursors of anti-inflammatory prostaglandins
      (PGE3) and inhibits the production of AA and the synthesis of thromboxane. Importantly, the
      amount of ALA converted to EPA and DHA in humans is usually low which makes also these fatty
      acids essential. The current western diet is poor of n-3 PUFAs and this suggests that n-3
      PUFAs-dependent endogenous anti-inflammatory mechanisms could be potentiated by
      simultaneously increasing n-3 PUFA intake and lowering the n-6/n-3 ratio. Indeed, a high
      n-6/n-3 ratio is associated to a worse clinical course in cardiovascular, inflammatory and
      autoimmune diseases. With the rationale of increasing n-3 PUFAs intake and of lowering the
      n-6/n-3 ratio, n-3 PUFAs supplementations like fish oil have been given with favorable
      clinical results to patients affected by different chronic inflammatory diseases including
      rheumatoid arthritis, inflammatory bowel disease, and psoriasis. Fish oil, however, has a low
      palatability and this may cause a low patients' compliance during prolonged therapy. Since
      seafood, and several fruits and vegetables have a high content of n-3 PUFAs, dietary regimens
      based on these specific foods are expected to increase n-3 PUFAs intake., thus representing
      an attractive alternative to the administration of exogenous fish oils products in
      therapeutic programs aimed to exploit the beneficial n-3 PUFAs effects in systemic
      inflammatory disorders.

      Therefore, the investigators explored the effect of a diet based on food with a high n-3 and
      low n-6 PUFAs content in long-term kidney transplant recipients. These patients could benefit
      from an increase in n-3 PUFAs intake because a persistent systemic inflammatory status occurs
      after kidney transplantation, that greatly contributes to the development of cardiovascular
      diseases and of chronic allograft dysfunction. Previous studies showed that dietary
      administration of n-3 increases graft survival in different animal models of organ
      transplantation, whereas n-6 PUFAs had opposite effects. Recently, the efficacy of n-3 PUFAs
      supplementation with canola oil in decreasing systemic inflammation and in lowering the
      incidence of rejections was demonstrated also in humans.
    

Intervention name(s): n-3 rich diet; Usual diet
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): This dietary plan included seafood (salmon, sardines, herrings, and bluefish) and specific fruits and vegetables (oranges, strawberries, cherries, bananas, courgettes, artichokes, mushrooms, cauliflowers and pumpkins). Olive oil, rich in monounsaturated fats, was also included in the dietary plan. Patients were encouraged to use n-3 rich margarine as additional source of fatty acids. According to the data of the manufacturer, the fatty acid composition of this margarine was 3.4 mg of n-3 and 7.8 mg of n-6 per 100 g of weight. To keep n-6 PUFA intake low, patients were also requested to eat less eggs, meat, whole grains and cereals. All the components of the diet were fresh foods, with the exception of salmon and herrings that could also be preserved. Because no change in body weight was requested, patients maintained the same energy and protein intake of the diet that they assumed before entering the study.; Usual diet of the patients
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment