My Notes for More on Lipids (Oley 2016 conference)
This is a presentation by Kara Caulkins, MD, MS from the 2016 Oley conference. She is a neonatologist and is presenting about the options for IV/TPN lipids in the US as well as their hepatotoxicity (harm to the liver). She is specifically talking about children, however much of this information can be generalized to adults, but there may be some differences that are significant. This is also an insurance issue as some of the lipid options are FDA approved for adults but not children.
TPN is composed of sugar, amino acids, vitamins and minerals, and lipids (fats). The lipids are an important component and provide a dense source of calories as well as essential fatty acids (EFAs) which are nutritionally necessary. EFAs are important for making hormones including anti-inflammatory ones (EFA deficiency can occur with people on TPN, which can lead to neurodevelopmental problems in children as well as vision problems). Long-term use of TPN (they think especially due to the lipids) is associated with liver disease and the the development of Intestinal Failure Associated Liver Disease (IFALD) which can progress to liver failure.
The most commonly used lipid source for TPN in the US right now is Intralipid which is entirely soy based. There are several other brands that are used mostly outside the US but can sometimes be used in the US, particularly on a compassionate use basis. Omegaven is one of these options and is entirely derived from fish oil. Another brand called SMOFlipid is a mixture of the two. A recent study found that for children who had developed IFALD, switching them to fish oil based lipids reversed the liver disease. This finding has been replicated several times. In one case children with advanced liver disease had the disease completely reversed within 9 to 12 weeks of being switched to fish oil based lipids from the soy-based ones.
So the question is why are Omegaven and fish oils so helpful. Fish oil contains high amounts of EPA and DHA, omega-3 EFAs which are anti-inflammatory. Soybean oil instead has high amounts of omega-6 fatty acids which are pro-inflammatory. Omegaven also has a high amount of vitamin E which is a powerful anti-oxidant and nutrient. Fish oil also lacks the phytosterols completely which seems to be the component in Intralipid that causes so much harm to the liver.
At 8:45 into the video there is a graphic showing the composition of specific lipids in both Intralipid and Omegaven.
Further studies have shown that children switched to fish oil lipid sources have lower levels of inflammation. Part of why this happens is because of the effects of different oils on the production of cytokines (which are cell-signalling molecules that regulate inflammation). Specific cytokines have been found to be directly related to the development of biliary problems such as "sludgy bile" and liver and gallstones. It's also known that long-term consumption of omega-3 EFAs is associated
with better health outcomes in general including lower rates of cancer,
heart disease, and other major illnesses.
Different oils can have very different amounts of what are called phytosterols, which are plant-based sterols (similar to cholesterol which is an animal-based sterol). When food containing phytosterols is consumed orally only a tiny fraction of the phytosterols is absorbed (and easily excreted). However, if lipids containing phytosterols are infused, this results in a high amount in the blood and is toxic to the liver. It's been known for decades that for people on IV lipids there is a direct correlation between higher levels of phytosterols in the blood and rising markers of liver disease. One mechanism of this is that inflammation and phytosterols inhibit the excretion of bile and bilirubin.
Ideally, a lipid source for infusion would have a ratio of types of fatty acids that is balanced (about 2 to 1 omega-3s to omega-6s), as well as little or no phytosterols, and a high amount of a good quality anti-oxidant such as vitamin E. The vitamin E should be primarily the alpha form of vitamin E (what vitamin E Intralipid has is mostly in the gamma form). Alpha vitamin E is included in the multivitamin that is added to TPN so that even people on Intralipid do get some of it.
Omegaven is not yet FDA approved so it is only available in the US either on a compassionate use basis or as part of a clinical trial. Over the last 10 years access to Omegaven has improved somewhat but is still very limited. There are also several lipid brands that are mostly olive oil or coconut oil which might be an option for patients who are allergic to both soy and fish, and some of these are FDA approved for adults.
