Lipid administration has little influence on nitrogen loss if it is not supplemented with glucose and proteins. Lipids must be prescribed to avoid deficits in essential fatty acids. New, energetic substrates, such as polyunsaturated omega-3 fatty acids (PUFAs), ornithine-ketoglutarate acid (OKGA), medium-chain triglycerides (MCT), short-chain fatty acids (SCFAs), and glutamine are suggested in order to modulate the different stages of cachexia (Fig. 2).
Hypocholesterolaemia and hypertriglyceri-daemia are frequently observed in wasting syndrome and are associated with a poor prognosis. Derangement of serum lipids and a reduction of body fat deposits are consequences of impaired food intake and reflect a series of metabolic disturbances, mainly due to alterations in TNF, inter-leukin (IL)-1, IL-2, IL-6, interferons (IFNs), and other cytokines.
A reduced supply of n-6 PUFAs and an increased supply of omega-3 fatty acids (m-3FAs) may reduce the inflammatory cascade of cytokine production. This effect seems to be due to eicos-apentaenoic acid (EPA), C20:5, n-3 and docosa-hexaenoic acid (DHA), C22:6, n-3, the main component of fish oil that decreases plasma triglycerides and VLDL while increases levels of LDL-cholesterol. In contrast to other fatty acids of the n-3 and n-6 series, EPA is a direct suppressant of lipid mobilisation factor in both in vitro and in vivo studies; it also counteracts weight loss, lipoly-sis, and protein catabolism as well as tumour growth .
Plasma levels of m-3FAs are inversely associated with the risk of coronary heart disease (CHD), blood pressure, renal PGE2 production, as well as IL-1, IL-2, IL-6, and TNF production by mononu-clear cells. Fish oil also protects the liver from reperfusion injury by reducing the synthesis of vasoconstrictive eicosanoids (from arachidonic acid). Weight gain has been reported in rats fed with fish oil.
Since m-3FAs are precursors for eicosanoids and any increase in the amount of n-3 family compounds in the diet produces some biological effects, with clinical implications in anorexia-cachexia syndrome, we studied  the effect of 10 g of fish-oil m-3FAs/day in AIDS patients who lost > 10% of their usual weight and who had elevated TGs and TNF, and hypocholesterolaemia. The study was a pilot, unblinded, randomised comparison between a dietary regimen containing 10 g of fish oil daily for 30 days and an equivalent dietary regimen without fish oil.
The study included 20 cachectic AIDS patients (stage IV C) who had lost > 10% of their usual weight in the 3 months prior to the beginning of the
study and who had hypertriglyceridaemia, hypoc-holesterolaemia, and elevated plasma TNF levels. The subjects (12 men and 8 women, age 30-37 years, mean 33.6 years) were weighed, measured (body circumferences and skinfold thickness) and randomly allocated to receive a personalised hyper-caloric-hyperproteic diet with or without fish oil.
All patients were under antiretroviral treatment and secondary prophylaxis for opportunistic infections (6 for MACD, 3 for neurotoxoplasmosis, 5 for PCP, 3 for CMV, 3 for candida). Patients with intractable diarrhoea, acute opportunistic infections, and/or a Karnofsky score < 50 were excluded. The caloric needs were calculated for each patient according to a modified Harris-Benedict equation, and extra calories were prescribed in relation to the patient's clinical condition. Caloric intakes was registered by means of a dietary questionnaire. TNF levels, anthropometric parameters, and clinical and laboratory data were determined at baseline and after 30 days.
One gram fish oil pills containing 18% EPA and 12% DHA as their ethyl esters, with 3 mg vitamin E per gram as antioxidant were provided by Novartis, Italy.
In our patients FO reduced the high levels of TNF, which allowed utilisation of TGs for liposyn-thesis and thus as energy for physical activity. It may well be that the entire cytokine network, the dysregulation of which may be involved in AIDS progression, responds to FO administration.
PUFAs serve as substrates within inflammatory cells for the formation of eicosanoid mediators. Eicosanoids derived from 20:omega-3 PUFAs (EPA,
DHA) are less proinflammatory and vasoactive than those derived from arachidonic acid (20:4 omega-6) and linoleic acid (18:2 omega-6) via the cyclooxyge-nase and lipooxygenase pathways.
Dietary FO inhibits 6-6-desaturase and cyclooxygenase, thereby reducing the metabolism of linoleic and arachidonic acid and the production of their derivatives eicosanoids, PGE2, TXA2, and TXB2. The addition to FO of vitamin E as antioxidant may be beneficial, because vitamin E supplementation per se reduces TNF and IL-6, which are well-known enhancers of HIV replication in macrophages/monocytes.
The clinical conditions of the subjects in the two groups were comparable at entry but, at the end, only those who received fish oil showed statistically significant improvements in the studied parameters. The mean weight gain was 2.4 kg; lean and fatty body masses, respectively, increased 1.4 and 0.67 kg; TGs decreased from 230 to 149 mg/dl; and cholesterol increased from 169 to 200 mg/dl. TNF levels decreased from 360 to 88 pg/ml. Caloric intake went from < 1550 Kcal/day to > 2200 Kcal/day.
The subset of AIDS patients affected by wasting syndrome with high levels of triglycerides and TNF and low cholesterol may benefit from a diet supplemented with adequate amounts of fish oil containing n-3 PUFA, which decrease the production of inflammatory cytokines and of futile metabolic cycles.
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