The FAP Gene Support Group

(Familial Adenomatous Polyposis)

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Alfa Capsules - Omega 3 Information

"You are what you eat!" Much has been said and written about how changing diets in developed countries over recent decades are having a significant impact on health. Two recent reports 1 have focused on how diet may affect mental health but there are implications too for cardiovascular disease, rheumatoid arthritis, inflammatory bowel disease and a range of cancers, including bowel cancer.

One aspect of diet that receives particular attention is the consequence of reduced consumption of oily fish. Why is that important? Oily fish contain particular types of fat, called long chain polyunsaturated fatty acids (PUFAs) that are essential to good health. They are essential because they playa key role in metabolism but cannot be made readily by the body and so must be consumed in as part of the diet. They originate in the plankton which fish ingest and are retained in various organs. Oily fish such as mackerel, herring, sardines and salmon contain the highest amounts. These PUFAs include the so-called omega-3 fatty acids, such as eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). Many diets have adequate or even excess amounts of the omega-6 group of PUFAs but are deficient in the omega-3 group.

There is mounting evidence to suggest that omega-3 PUFAs, in particular EPA, can prevent the promotion and progression of certain cancers. These effects are believed to result from changes in the immune response, changes in metabolism, cell growth and differentiation and in apoptosis. Apoptosis is a normal physiological process of programmed cell death and is important in maintaining normal levels of healthy cells, for example those in the mucosa lining the gut.

Bowel cancer is thought to develop as a result of an imbalance between the production of new cells and programmed cell death in the lining of the gut. This leads to the formation of polyps (small growths projecting into the gut) and an increased likelihood of cells having faulty DNA. Some of these polyps may then develop into cancer. A number of studies have shown that supplementing the diet with fish oil can redress this imbalance in patients with occasional (sporadic) polyps, who have an increased risk of bowel cancer compared to the general population.

Government bodies are keen to encourage greater consumption of oily fish to increase the intake of omega-3 PUFAs but we are advised also to limit the amount to about two portions per week. The reason for these mixed messages is that, whilst fish are good at accumulating the essential PUFAs, they also accumulate potentially harmful environmental pollutants such as pesticides, dioxins and heavy metals such as mercury.

How can we resolve the dilemma of increasing the intake of essential omega-3 PUFAs and concerns over environmental contaminants in fish? There is increasing interest in supplementing the diet with fish oils. However, many of these contain mixtures of PUFAs and care must be taken to ensure that the contaminants are removed. Also, as mixtures of fatty acids, it is necessary to take large numbers of capsules in order to absorb sufficient amounts of the important PUFAs such as EPA in order to make a difference.

S.L.A. Pharma AG is addressing these problems by developing a pure form of EPA (ALFA). This is extracted from high quality fish oils and contains 99% EPA which is converted to the free fatty acid. This free fatty acid is very much more readily absorbed than the naturally-occurring forms (ethyl ester or triglyceride) found in most fish oil supplements. Furthermore, it contains very low levels of environmental contaminants. It is taken in specially designed capsules which release their contents
in the small intestine, avoiding the fishy aftertaste and abdominal discomfort experienced with some fish oil preparations.

S.L.A. Pharma is currently investigating the potential benefits of ALFA in patients with sporadic polyps. In a recent study in patients with a history of sporadic polyps, EPA 99% taken for a period of 3 months produced marked reductions in cell proliferation and an increase in apoptosis in the lining of the colon2. This effect would be expected to reduce the likelihood of formation of polyps (and hence cancer) in the large bowel. Importantly, this response was achieved with ALFA in 3 months. This contrasts with results from a similar study in Japan in which a mixture of EPA and DHA, taken as 8 capsules per day for 2 years, caused an increase in apoptosis after 24 months but not after 12 months3. This suggests that ALFA may have a much more rapid effect.

The next steps will be to find the optimal dose to produce these changes and then to see whether ALFA reduces the development of polyps in patients with Familial Adenomatous Polyposis (FAP). Given the large numbers of polyps that form in gastrointestinal tract in this condition there is a well recognised high risk of developing bowel cancer. Whilst colectomy remains the most effective preventative measure, any additional intervention that prevents or reduces the rate of development of polyps would be welcome.

Readers may be familiar with the group of drugs called COX-2 inhibitors, such as celecoxib and rofecoxib, which showed considerable promise in preventing the development of polyps in patients with FAP. Unfortunately, they were found subsequently to be associated with an increased risk of heart problems and so their use is now restricted. EPA 99% offers the possibility of achieving similar benefits but with a greatly reduced risk of undesirable effects in patients at risk of bowel cancer and we await the outcome of further clinical trials with interest.

1 Feeding Minds - the impact of food on mental health (The Mental Health Foundation; January 2006) Changing Diets, Changing Minds: how food affects mental well being and behaviour (Sustain; January 2006).

2 Courtney, Matthews, Finalyson, di Pierro, Belluzzi, Roda, Kang & Leicester (submitted for publication).

3 Cheng, Ogawa, Kuriki et a/., (2003) Cancer Letters; 193:17-24.