Boning Up on Fats and Skeletal Health (Part Two): Omega-3 and Omega-6

Reading Time: 11 minutes

In this second installment on fat intake and bone health, we examine more closely the effect of omega-3 and omega-6 fatty acids. The quantities, ratios and source of these fats in your diet could have pronounced impact on how much inflammatory damage your bones are exposed to.

Key Points:

  1. Omega-3 fatty acids potentially help maintain bone mineral density and strength through their anti-inflammatory effects. However, the research is not unanimous in this view.
  2. Consuming omega-3’s in conjunction with calcium and other bone-supporting nutrients or in fish, seem to enhance their beneficial impacts.
  3. Research is conflicting, though it appears that a low level of omega-6 intake is protective, but consuming high amounts may cause inflammatory breakdown of bones. This may be a particular issue when omega-6’s far outweigh omega-3’s in the diet, as is common in the modern western diet.

First, let’s bone up on omega-fatty acid basics.

There are a number of Polyunsaturated Fatty Acids out there. Some of the key ones are: 

Essential Short Chain Fatty Acids: Essential because they can’t be produced in our own bodies

  • alpha linolenic acid (ALA, an omega-3) 
  • linoleic acid (LA, an omega 6)

And,

Long Chain Fatty Acids

  • EPA and DHA (omega 3)
  • AA (omega 6)

The long chain fatty acids can be obtained from the diet, or synthesised from the short chain fatty acids. 

In order to be converted into longer chain fatty acids,  LA and ALA compete for the same pool of elongase and desaturase enzymes. The conversion is quite inefficient, which is why only approximately 21% of ALA is converted into EPA, and 9% into DHA. It seems high intake of omega-6 fatty acids (eg: most western diets) also limits conversion of ALA into EPA or DHA. More on this next week.

Significance of PUFA’s to bones

PUFA’s are primary precursors of eicosanoids- i.e. signaling molecules such as prostaglandins which affect many cells and cell-to-cell interactions. The long chain PUFA Arachidonic Acid (AA) can be converted into prostaglandins which promote inflammation (and can increase bone breakdown). In contrast, EPA (& DHA) (long chain omega 3’s) are precursors for anti-inflammatory prostaglandins (which inhibit bone breakdown). In order to be converted to their respective prostaglandins, each of these fatty acids have to compete with each other for the same enzyme. However, the enzyme preferentially reacts with AA- meaning inflammatory prostaglandins are preferentially produced.

Omega-3’s and bones

Omega -3’s have been known for their anti-inflammatory benefits elsewhere (eg: the cardiovascular system). You can probably add bones to that list. 

First of all, there has been an association observed between omega 3’s, bone mineral density and markers of bone turnover in many- but not all- studies. For example, blood levels of omega-3’s have been positively correlated with the greater lay down of minerals in bone of both mice and humans. One study (conducted only among Spanish women) found an interesting association between a high intake of long-chain omega 3’s and bone mineral density at the hip among ‘healthy’ women… but not osteoporotic women. IF found to be a true, repeatable finding representative of broader populations (it isn’t yet), this could affect when increasing omega-3 intake would be recommended, and by how much. 

Other observational studies have explored overall omega-3 intake and osteoporotic fracture risk/prevention. Mixed results regarding their association have been found. This is despite some of the studies assessing thousands of people, which generally increases the strength of associative data.

Conflicting data has also been obtained regarding the association between individual omega-3 fatty acids and fracture risk. 

Image credit: Julia Mikhaylova at bigstock.com

As we say in the biz, correlation is not causation, and harder evidence is required. This has been partially provided by cell culture and animal studies that affirm the power of omega-3’s. However, human studies are few in number and have produced conflicting results. Limitations such as study design and use of non-homogenous populations also mean they don’t allow strong conclusions to be drawn.

For example, a 2012 systematic review explored 10 randomised controlled trials involving: omega-3 fortified foods, supplements or diet modifications- either alone or in conjunction with other vitamins/minerals. Of these 10 trials, only four reported significant favorable effects of omega-3 fatty acids on bone mineral density or bone turnover markers. Plus three of these four delivered the omega-3’s in combination with high calcium foods or supplements. Thus the effect of omega-3’s is not indisputable, and it appears that any potential benefit may be enhanced when paired with calcium… this review also suggested combining it with other vitamins and minerals and/or mixtures of other concentrated oils could enhance the benefit.  

A 2019 meta-analysis highlighted a 2.6% increase in bone mineral density of the lumbar spine resulting from increased omega-3 intake- however the evidence producing this statistic was of “low-quality”. The evidence was even poorer for fracture incidence, upper femur bone mineral density and total bone mass- hence effects may be either unclear or null. 

Other studies blatantly challenge the view that omega-3’s support bone health. For example, 2 whole years of omega-3 fish oil supplementation (providing 4.5g EPA and DHA/day, a level well above recommendations for general and cardiovascular health), did not alter bone loss among men and women with knee osteoarthritis. Even when the data was adjusted for potential confounding factors (such as age, gender, study centre and uses of bone-related drugs) no effects were seen. Yes- osteoporosis and osteoarthritis are two distinct conditions, however the study was performed in a group (>55 years of age) who are sensitive to bone loss & factors mediating this. 

On the plus side, the studies that don’t show a benefit generally show a null effect- so at least we know omega-3’s don’t harm bone health! 

The early research focused most on omega 3’s and general indicators of bone health. A 2017 study aimed to advance beyond this and identify whether there is any specific effect on fracture healing. The mice model they used was affirmative- omega-3’s accelerated healing. However, they could not show HOW. Also, an issue with this study is that they used the results to support the argument that supplementation with omega 3’s may help fracture healing. The problem with this is that their model used mice who’ve been genetically altered to allow them to convert omega 6’s to omega 3’s, rather than receiving the omega 3 intake through diet. This conversion is something we humans simply cannot do, and we can’t be absolutely certain that omega-3’s consumed orally would have identical effects. 

If Omega-3’S help bones… how?

Explanations of possible mechanisms expand on what we said earlier and in Part One about inflammation. The long-chain EPA & DHA are precursors for prostaglandins and other anti-inflammatory eicosanoids. 

They can also lower levels of inflammatory (omega-6 derived) prostaglandins and interleukins within the blood. These substances have been shown to increase bone breakdown within lab studies. At the same time, omega-3’s can boost production of insulin-like growth factors, which stimulate bone remodelling, and increase calcium absorption from the gut. More bone formation markers are found in the blood. 

Image credit: Richman Photo at bigstock.com

Another interesting observation is that they seem capable of hindering the activity of bone-degrading cells. This comes from cell culture studies. The long-term impact of this on the strength of your bones- in situ within the body- has not been verified, though. 

Animal and cell culture studies suggest that omega-3’s delivered in conjunction with calcium may enhance calcium absorption from the small intestine and reduce urinary calcium excretion. Randomised Controlled Trials have shown improved indicators of bone health with the combination. Essential fatty acids assist vitamin D in calcium absorption. 

Fish intake and bones

Observational and randomised controlled trials generally suggest getting your omega-3’s through through fatty fish is a good way to go. They link high fatty fish intake and lower risk of fractures. Fatty fish are those with dark flesh, for example salmon, sardines, swordfish, and mackerel- containing approximately 2.5 grams of EPA and DHA per 100 grams. (Keep in mind each species will provide differing amounts). 

However, there are also some studies which cast doubt over the relationship between fish intake and bone mineral density. This may possibly be explained by poor standards of documentation for fish varieties consumed. As always, the only way to be sure is with more, better research. 

Any bone-related benefit from fatty fish may be related not only to the EPA & DHA contents, but also the good vitamin D supplies, and other nutrients found within fatty fish.

Interestingly, a large cross-sectional study in Norway linked a high intake of fish, in particular lean fish, with bone mineral density in older women. Did you notice the kicker? Yes: the association was particularly strong with lean fish, i.e. those with low levels of omega-3’s… whereas no association was seen between intake of fatty fish and bone mineral density in men or women, whether middle aged or elderly. One possibility is that this is inaccurate: assessing dietary intake with self-report food frequency questionnaires such as those used in this study is not immune to errors. Or there may be something else going on… Perhaps the non-fatty fish contain higher levels of other nutrients helpful to bone mineral density, or there is another bone-promoting characteristic common to the lean-fish-loving group that was not documented. Or perhaps the intake of omega-3’s truly had no impact in this study population…

In summary, overall it seems omega-3’s may improve bone mineral density to some degree, but high-quality human randomised controlled trials are needed to determine to what degree, how much is required, and the optimal way to take them. 

In the meantime, I’d suggest aiming for the intake generally recommended by other health bodies. This advice includes having fatty fish at least twice a week. There are no recommended daily intakes for the polyunsaturated fatty acids, however the health bodies of Australian and New Zealand governments suggest Adequate Intakes, and the Australian Heart Foundation also provides recommendations which are believed to be appropriate for bone as well as heart health. See below for these precise recommendations. 

Omega-3’s: recommendations and food sources

ALA:
NHMRC Adequate intake: 1.3 g/day (men), 0.8g/day (women)
Food sources: walnuts, linseed (otherwise known as flaxseed) & linseed oil, chia seeds, hemp seeds, canola oil, soybean oil, edamame, navy beans, avocados

EPA & DHA:
NHMRC Adequate intake: 160mg/day (men), 90mg/day (women)
Australian Heart Foundation recommendations: 250-500mg/day
Food sources: fish and seafood, especially dark-flesh/fatty fish

Omega-6’s and bones

There is little data available for the effect of linoleic acid on bone cells. However, as mentioned earlier, linoleic acid can be converted to arachidonic acid (AA), which is the major omega-6 precursor of inflammatory eicosanoids such as prostaglandins, thromboxanes, and leukotrienes. These can impede fracture healing.

Mechanisms are believed to include inhibition of the growth, spread, metabolism and activity of bone-forming cells. This has been observed in cell cultures. Exposure to  AA has also been shown to aid in the production of numerous pro-inflammatory cytokines.

However, we can’t simply classify omega-6’s as bone degrading. A large observational study has suggested consuming >6.8 g of linoleic acid per day- possibly up to 12.1 g/d- may actually be beneficial. Yet another large observational study has suggested that a higher intake of total omega-6’s, when combined with a higher alpha linolenic acid intake, is associated with a reduced risk of fracture.

In addition, some in-vitro studies from animal cells suggest that while high levels of AA-derived prostaglandin can inhibit bone growth, low levels can actually stimulate it. However, studies on human cells leave more room for confusion. This needs to be clarified. 

In view of this uncertainty, it is best to aim for an intake inline with general-health recommendations:

Linoleic acid (omega 6)
 NHMRC Adequate intake: 13 g/day (men),  8g/day (women)
Food sources: vegetable oils (eg: sunflower, safflower, soybean, corn, canola), nuts, seeds, meats, dairy and eggs.

With all this conflicting information, some have suggested that rather than looking at total omega-3 or omega-6 intakes alone, we should instead consider…

Omega-6: omega-3 ratios

We have reason to believe that the typical modern Western diet provides significantly more omega-6 fatty acids, relative to omega-3’s, than it did in the past. It is thought that “once upon a time” the omega-6: omega-3 ratio may have been something like 1:1, whereas now it’s more like 15:1. There is also some reason to believe that this shift has been pro-inflammatory. 

Indeed, lower ratios of omega-6’s to omega-3’s in the diet appear to decrease osteoporotic risk and decelerate bone loss after menopause. Likewise, a lower ratio within the blood has been associated with better bone mineral density. However, we have very little quality evidence from randomised controlled trials to back these associations up. Also, no dose-response can be verified and so the optimal ratio is unknown. In the face of this, a 10:1 ratio for women and a 8.75:1 ratio for men has been a recent recommendation… but this may be updated in time. 

Hormone therapy, PUFA’s & bone density

Many women receive hormone replacement therapy (HRT) to manage post-menopause. This can go some way to preserving skeletal health, and so their bones may respond to PUFA’s differently to post-menopausal women not on HRT.  There is some conflict between the results of different studies in this area, and so further, rigorous controlled trials should be performed.  

Something smells fishy… in the research

We’ve discussed some weaknesses already, such as small sample sizes, and over-reliance on associations. However, there are other factors undermining the strength of our findings- such as the studies being too brief to determine long-term effects. In addition, racial backgrounds tend to affect bone health (white women have an approximately 60% higher risk for hip fractures than black women and 75% higher than Asian/Pacific Islander women). Yet, we have no information on whether race also alters the effect of fat intake on bones, and most studies don’t even report these demographics. 

Research could perhaps also be improved by using tools other than bone mineral density, bone metabolism markers and fracture incidence to assess bone health. It has been observed that most fragility fractures occur in people whose Bone Mineral Density doesn’t classify them as osteoporotic. The WHO has developed a risk fracture assessment tool, FRAX, which is considered superior in determining people’s 10-year major osteoporotic and hip fracture probability, 

The Verdict

We have not yet reached a consensus on the effect of higher levels of total PUFA, omega-3, omega-6 and omega-6:omega-3 ratios, due to limited data or low quality research. 

In the face of this, I would recommend consuming omega-6’s through vegetable oils (eg: sunflower, safflower, soybean, corn, canola), nuts, seeds, meats, dairy and eggs, but be sure to also regularly include omega-3 sources such as linseed, chia seeds, hemp seeds, canola oil, soybean oil, edamame, navy beans, avocados and fish. At this stage, it seems it is advisable to obtain your EPA & DHA by regular consuming fish and seafood- rather than omega-3 supplements. This is because: a) currently the strongest evidence for benefits comes from studies of fish intake, and b) fish can also provide useful protein, vitamin D, calcium, and other vitamins and minerals that help maintain strong bones. 

As the body of research becomes stronger,  these recommendations may be adjusted and/or made more specific for the different fats and/or different scenarios. 

What change could you make to promote your bone health? Feel free to comment below. 

References

Abdelhamid, A., Hooper, L., Sivakaran, R. et al. (2019) The Relationship Between Omega-3, Omega-6 and Total Polyunsaturated Fat and Musculoskeletal Health and Functional Status in Adults: A Systematic Review and Meta-analysis of RCTs. Calcif Tissue Int 105, 353–372  https://doi.org/10.1007/s00223-019-00584-3.

Chen, Y., Cao, H., Sun, D., Lin, C. et al.(2017). Endogenous Production of n-3 Polyunsaturated Fatty Acids Promotes Fracture Healing in Mice. Biomechanics in Musculoskeletal Health. Article ID 3571267. https://doi.org/10.1155/2017/3571267.  

Chen, J.S., Hill, C.L., Lester, S. et al. (2016) Supplementation with omega-3 fish oil has no effect on bone mineral density in adults with knee osteoarthritis: a 2-year randomized controlled trial. Osteoporos Int 27, 1897–1905. https://doi.org/10.1007/s00198-015-3438-x

Harris, M., Farrell, V., Houtkoope, l.L., Going, S., and Lohman, T. (2015), Associations of Polyunsaturated Fatty Acid Intake with Bone Mineral Density in Postmenopausal Women. Journal of Osteoporosis. Article ID 737521. 8 pages. https://doi.org/10.1155/2015/737521

Heart Foundation (2015), Fish and Omega-3: questions and answers for health professionals.  https://www.heartfoundation.org.au/getmedia/741b352b-1746-48f4-806a-30f55fddfad2/Health_Professional_QA_Fish_Omega3_Cardiovascular_Health.pdf

Karpouzos, A., Diamantis, E., Farmaki, P., Savvanis, S., and Troupis, T.  (2017). Nutritional Aspects of Bone Health and Fracture Healing. Journal of Osteoporosis |Article ID 4218472 | 10 pages | https://doi.org/10.1155/2017/4218472

Longo, A.B., and Ward, W.E. (2016). PUFAs, Bone Mineral Density, and Fragility Fracture: Findings from Human Studies, Advances in Nutrition, 7(2), Pages 299–312, https://doi.org/10.3945/an.115.009472

Longo, A.B., and Ward, W.E. (2016) PUFAs, Bone Mineral Density, and Fragility Fracture: Findings from Human Studies. Advances in Nutrition, 7(2): 299–312. https://doi.org/10.3945/an.115.009472

Lavado-García, J., Roncero-Martin, R., Moran J.M., et al. (2018) Long-chain omega-3 polyunsaturated fatty acid dietary intake is positively associated with bone mineral density in normal and osteopenic Spanish women. PLOS ONE 13(1): e0190539. https://doi.org/10.1371/journal.pone.0190539

Orchard, T.S., Pan, X., Cheek, F, Ing, S.W., and Jackson, R.D. (2012). A systematic review of omega-3 fatty acids and osteoporosis. British Journal of Nutrition 107, S253–S260.doi:10.1017/S0007114512001638 

Rosendahl-Riise, H., Karlsson, T., Drevon, C.A. et al. (2019). Total and lean fish intake is positively associated with bone mineral density in older women in the community-based Hordaland Health Study. Eur J Nutr 58, 1403–1413. https://doi.org/10.1007/s00394-018-1665-6

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