From alpha to omega

Should we eat flax seed? 

Back in 1999 a group of scientists took some rats with polycystic kidneys and fed them a diet supplemented with flaxseeds. (Ogborn, 1999) The results were that they (the flax-eating-rats) had lower creatinine levels and less cystic change than rats fed a normal diet. However, subsequent studies have produced inconsistent results and a Cochrane review in 2005 stated that there was insufficient evidence to rule one way or another whether supplementing diet with omega-3 fatty acids was beneficial in kidney disease.

Since then at least two papers (Tou, 2015 and Ogborn, 2006) have strongly suggested that a diet rich in flax seeds will attenuate the progression of polycystic disease of the kidneys (PKD).

Flax seed: rich in alpha-linolenic-acid, an omega-3 fatty acid.

Some background:
Flax Seeds
The flax plant has the apt Latin name Linum usitatissimum, meaning “very useful”. Flax seed is the same as linseed, the latter name applied more when the oils are used for industrial processes – linseed oil on the furniture. US can thank the colonists for bring flax across the Atlantic, for now it is the main source of the essential fatty acid Alpha-linolenic-acid (ALA).

Alpha linolenic acid (ALA)
Without delving too deeply into biochemistry, ALA is an essential fatty acid. Yes, it is a fat, but it’s a good one. A fatty acid is a chain of carbon atoms with a “carboxyl group” attached to a long aliphatic tail. Fatty acids are important for making cell membranes – the aliphatic tail hates water so when two layers of phospholipids get together the tails point inwards and hang onto each other giving them some protection from the water content of the cells.

An “essential” fatty acid is one that the human body cannot make internally for itself so it must be present in the diet.

Each carbon atom in the chain on the fatty acid has four bonds and if all four are used up or joined to other atoms then the fat is said to be “saturated”. Some of the bonds may not be utilised, in which case they hold hands lightly with the adjacent carbon atom but are ready to let go for certain other atoms – fats with double bonds like this are called “unsaturated”.
The carbonyl head of the fatty acid is known as the alpha end while the other end of the chain is the omega end. Omega-3 fatty acids are ones with a double bond on the third carbon from the omega end. They are also called n-3 fatty acids. You will find “omega-3” used more in nutritional literature and “n-3” in technical documents. So alpha LINOLENIC acid (ALA) is an omega-3 fatty acid. It is not the same as LINOLEIC acid (LA) which is an omega-6 fatty acid – the double bond on the sixth carbon atom from the end.

One other thing that is useful to know is that most natural fatty acids will be in the “cis” position which makes the long tail curved, but some processes, specifically those used in preserving foods, will change the shape to the “trans” position so the tail is fixed straight – these are known as “trans fats” and generally are not healthy because they increase the levels for LDL fats in the body, the bad ones. [As an aside here, in 1911 Crisco was the first hydrogenated fat sold for cooking, the company gave away cookery books to encourage its use – not until 2007 was this trans fat reformulated to a healthier recipe.]

The final piece of biochemistry in this jigsaw is to do with the pathways in the body by which fatty acids are processed. Omega-3 and Omega-6 fatty acids use the same metabolic pathways and so compete for attention. Omega-6 tend to win in this competition, they are slightly easier to process and usually more abundantly available. The end product for omega-6 is arachidonic acid (AA) which is a pro-inflammatory molecule, i.e. you don’t want too much floating around, while the end product for omega-3 fatty acids are the more healthy eicosanoids (EPA and DHA). Thus diets rich in omega-3 fatty acids are generally beneficial. They have conclusively been shown to lower blood pressure, reduce LDL lipid levels, reduce heart disease and reduce inflammation.

The Rats
All of these studies have been undertaken using rats rather than humans. This isn’t so strange because we share all but 1% of our DNA and are physiologically pretty similar. The rats used in the 1999 studies were “Han:SPRD-cy” rats. SPRD stands for a line of rats originally bred in the Sprague Dawley farms of Wisconsin in 1925, the Han indicating this particular strain was from Hannover laboratories.

Sprague Dawley Rats

The important part for us with ADPKD is the “cy” indicating these rats have polycystic kidneys. The genetic error in rats is not the same as the faulty genes in humans that produce ADPKD. But the illness progresses in a similar fashion to human polycystic kidneys. The earlier rats were known as “PKD” strain but later rats are “PCK” which may have more similarities pathophysiologically with human ARPKD. So if you are reading any papers on rat studies it is worth burrowing down to find out which strains were used.

The Studies
The first study I mentioned (Ogborn, 1999) simply fed half their rats, from birth, on a diet with 10% flax seed and half on a non-supplemented diet, standard rat-food I guess. For reasons not explained they only used male rats. After 8 weeks they examined kidneys for cysts and fibrosis and blood for creatinine and lipid levels. In the flax-fed rats there were fewer cysts, less inflammation in the tissue between the cysts and significantly lower creatinine levels. They also used a measure to reflect the proportions of omega-3 and omega-6 fatty acids found in kidney tissue, finding three times the amount of omega-3 in the flax-fed rats. Their conclusions were:

Flaxseed ameliorates Han:SPRD-cy rat polycystic kidney disease through moderation of the associated chronic interstitial nephritis. The diet alters renal content of polyunsaturated fatty acids in a manner that may promote the formation of less inflammatory classes of renal prostanoids.

Another study from 2003 (Lu, 2003) gave their rats a very high fat diet but varied the proportions to look at the effects of fish oil, soybean oil and cotton seed oil, They didn’t look at flax seed. However they did show that the omega-3 oils resulted in smaller kidneys and less fibrosis and higher creatinine clearance.

In 2006, Ogborn, who seems to produce a lot of papers on this topic, muddied the waters by announcing that male rats did not benefit as much as females from the omega-3 rich diets. This needs to be considered alongside the fact that male PKD rats have a more severe disease process than female PKD rats and this is one area which does not compare so neatly with human ADPKD.

Then we come to the paper that caught my interest and set me on the path to explore flax: a review article in a nutritional journal (Tou, 2015) that summarises its conclusions as

• ALA-rich flaxseed attenuated polycystic kidney disease progression.
• Soybean oil resulted in inconsistent renal effects.
• Anti-inflammatory EPA/DHA-rich fish oil attenuated polycystic kidney disease.
• Adverse renal effects due to DHA provided as algal oil raised safety concerns.

That first conclusion is a pretty bald statement. Yes it has been shown in rats and those rats are a reasonable model for human ADPKD, so my reading of this is that we would benefit from adding flax-seed to our diets.

One form of flax seed, which appears to have Biblical approval.

Flax seed
Of the fatty acids found in flax seed, 54% are ALA. The seed needs to be ground to release this amount. Interestingly, chia seed contains more ALA and doesn’t need to be ground but isn’t quite such a versatile food ingredient. Alternatively flax oil can be used, 15ml contains 8g ALA. Flax is also low in carbohydrate, high in fibre, contains vitamin E and is low in sodium.

I am currently exploring how to incorporate it into the diet – some suggestions such as spreading it on toast with honey really don’t appeal but it seems you can add it to casseroles, bread, cereal and even add it to smoothies. My husband is tolerating my experiments well, barring the rather gloupy lamb stew that was meant to be a Valentine’s Day lamb curry. It may be that we settle for the oil in a capsule with breakfast!

References: 

Lu et al. Detrimental effects of high fat diet in early renal injury are ameliorated by fish oil in Han:SPRD-cy rats. J Nutr 2003 Jan. 133(1):180-6

Ogborn MR, at al Flax seed ameliorates interstitial nephritis in rat polycystic kidney disease. Kidney Int 1999, Feb;55(2)417-23

Ogborn MR, Nitschmann E, Bankovic-Calic N, Weiler HA, Aukema H. Dietary flax oil reduces renal injury, oxidized LDL content, and tissue n-6/n-3 FA ratio in experimental polycystic kidney disease. Lipids. 2002;37(11):1059-65.

Ogborn MR, Nitschmann E, Bankovic-Calic N, Weiler HA, Aukema HM. Effects of flaxseed derivatives in experimental polycystic kidney disease vary with animal gender. Lipids. 2006;41(12):1141-9.

Tou J, Gigliotti JC, Maditz KH, Evaluating the therapeutic value of omega-3 polyunsaturated fatty acid supplementation on polycystic kidney disease and co-morbidities.
Food Microbiology, 2015, April (2) :20-28