MD, PhD, MAE, FMedSci, FRSB, FRCP, FRCPEd.

fish oil

The regular consumption of fish-oil has a potentially favourable role in inflammation, carcinogenesis inhibition and cancer outcomes. An analysis of the literature aimed to review the evidence for the roles of dietary-fish and fish-oil intake in prostate-cancer (PC) risk, aggressiveness and mortality.

A systematic-review, following PRISMA guidelines was conducted. PubMed, MEDLINE and Embase were searched to explore PC-risk, aggressiveness and mortality associated with dietary-fish and fish-oil intake. 37 studies were selected.

A total of 37-studies with 495,321 participants were analysed. They revealed various relationships regarding PC-risk (n = 31), aggressiveness (n = 8) and mortality (n = 3). Overall, 10 studies considering PC-risk found significant inverse trends with fish and fish-oil intake. One found a dose–response relationship whereas greater intake of long-chain-polyunsaturated fatty acids increased risk of PC when considering crude odds-ratios [OR: 1.36 (95% CI: 0.99–1.86); p = 0.014]. Three studies addressing aggressiveness identified significant positive relationships with reduced risk of aggressive cancer when considering the greatest intake of total fish [OR 0.56 (95% CI 0.37–0.86)], dark fish and shellfish-meat (p < 0.0001), EPA (p = 0.03) and DHA (p = 0.04). Three studies investigating fish consumption and PC-mortality identified a significantly reduced risk. Multivariate-OR (95% CI) were 0.9 (0.6–1.7), 0.12 (0.05–0.32) and 0.52 (0.30–0.91) at highest fish intakes.

The authors concluded that fish and fish-oil do not show consistent roles in reducing PC incidence, aggressiveness and mortality. Results suggest that the specific fish type and the fish-oil ratio must be considered. Findings suggest the need for large intervention randomised placebo-controlled trials.

Several other recent reviews have also generated encouraging evidence, e.g.:

Available evidence is suggestive, but currently inadequate, to support the hypothesis that n-3 PUFAs protect against skin malignancy.

…omega-3 fatty acids may exert their anticancer actions by influencing multiple targets implicated in various stages of cancer development, including cell proliferation, cell survival, angiogenesis, inflammation, metastasis and epigenetic abnormalities that are crucial to the onset and progression of cancer.

If I was aiming for a career as a cancer quack, I would now use this evidence to promote my very own cancer prevention and treatment diet. As I have no such ambitions, I should tell you that regular fish oil consumption is no way to treat cancer. It also is no way to prevent cancer. If anything, it might turn out to be a way of slightly reducing the risk of certain cancers. To be sure, we need a lot more research, and once we have it, fish oil will be entirely mainstream. Raising false hopes regarding ‘alternative cancer cures’ based on fairly preliminary evidence is counter-productive, unethical and irresponsible.

As I have said on several occasions before: I am constantly on the lookout for new rigorous science that supports the claims of alternative medicine. Thus I was delighted to find a recent and potentially important article with some positive evidence.

Fish oil has been studied extensively in terms of its effects on health. We know that it has powerful anti-inflammatory properties and might thus benefit a wide range of conditions. However, the effects of FO in rheumatoid arthritis (RA) have not been examined in the context of contemporary treatment of early RA.

A new study has tried to fill this gap by examining the effects of high versus low dose FO in early RA employing a ‘treat-to-target’ protocol of combination disease-modifying anti-rheumatic drugs (DMARDs).

Patients with RA <12 months’ duration and who were DMARD-naïve were enrolled and randomised 2:1 to FO at a high dose or low dose (for masking). These groups, designated FO and control, were given 5.5 or 0.4 g/day, respectively, of the omega-3 fats, eicosapentaenoic acid + docosahexaenoic acid. All patients received methotrexate (MTX), sulphasalazine and hydroxychloroquine, and DMARD doses were adjusted according to an algorithm taking disease activity and toxicity into account. DAS28-erythrocyte sedimentation rate, modified Health Assessment Questionnaire (mHAQ) and remission were assessed three monthly. The primary outcome measure was failure of triple DMARD therapy.

In the FO group, failure of triple DMARD therapy was lower (HR=0.28 (95% CI 0.12 to 0.63; p=0.002) unadjusted and 0.24 (95% CI 0.10 to 0.54; p=0.0006) following adjustment for smoking history, shared epitope and baseline anti–cyclic citrullinated peptide. The rate of first American College of Rheumatology (ACR) remission was significantly greater in the FO compared with the control group (HRs=2.17 (95% CI 1.07 to 4.42; p=0.03) unadjusted and 2.09 (95% CI 1.02 to 4.30; p=0.04) adjusted). There were no differences between groups in MTX dose, DAS28 or mHAQ scores, or adverse events.

The authors concluded that FO was associated with benefits additional to those achieved by combination ‘treat-to-target’ DMARDs with similar MTX use. These included reduced triple DMARD failure and a higher rate of ACR remission.

So here we have a dietary supplement that actually might generate more good than harm! There is a mountain of data of good research on the subject. We understand the mechanism of action and we have encouraging clinical evidence. Some people might still say that we do not need to take supplements in order to benefit from the health effects of FO, consuming fatty fish regularly might have the same effects. This is true, of course, but the amount of fish that one would need to eat every day would probably be too large for most people’s taste.

The drawback (from the perspective of alternative medicine) in all this is, of course, that some experts might deny that FO has much to do with alternative medicine. Again: what do we call alternative medicine that works? We call it MEDICINE! And perhaps FO is an excellent example of exactly that.

For this blog, I am constantly on the lookout for ‘positive news’ about alternative medicine. Admittedly, I rarely find any.

All the more delighted I was when I found this new study aimed to analyse the association between dietary long-chain n-3 polyunsaturated fatty acids (PUFAs) and incidence of rheumatoid arthritis (RA) in middle-aged and older women.

Data on diet were collected in 1987 and 1997 via a self-administered food-frequency questionnaire (FFQ). The risk of RA associated with dietary long-chain n-3 PUFAs and fish intake was estimated using Cox proportional hazard regression models, adjusted for age, cigarette smoking, alcohol intake, use of aspirin and energy intake.

The results show that, among 32 232 women born 1914–1948, 205 RA cases were identified during a mean follow-up of 7.5 years. An intake of dietary long-chain n-3 PUFAs (FFQ1997) of more than 0.21 g/day (lowest quintile) was associated with a 35% decreased risk of developing RA compared with a lower intake. Long-term intake consistently higher than 0.21 g/day (according to both FFQ1987 and FFQ1997) was associated with a 52% decreased risk. Consistent long-term consumption (FFQ1987 and FFQ1997) of fish ≥1 serving per week compared with<1 was associated with a 29% decrease in risk.

The authors concluded that this prospective study of women supports the hypothesis that dietary intake of long-chain n-3 PUFAs may play a role in aetiology of RA.

These are interesting findings which originate from a good investigation and which are interpreted with the necessary caution. As all epidemiological data, this study is open to a number of confounding factors, and it is therefore impossible to make firm causal inferences. The results thus do not led themselves to clinical recommendation, but they are an indication that more definitive research is warranted, all the more so since we have plausible mechanisms to explain the observed findings.

A most encouraging development for alternative medicine, one could conclude. But is this really true? Most experts would be surprised, I think, to find that PUFA-consumption should fall under the umbrella of alternative medicine. Remember: What do we call alternative medicine that works? It is called MEDICINE!

Many experts are critical about the current craze for dietary supplements. Now a publication suggests that it is something that can save millions.

This article examines evidence suggesting that the use of selected dietary supplements can reduce overall disease treatment-related hospital utilization costs associated with coronary heart disease (CHD) in the United States among those at a high risk of experiencing a costly, disease-related event.

Results show that:

  • the potential avoided hospital utilization costs related to the use of omega-3 supplements at preventive intake levels among the target population can be as much as $2.06 billion on average per year from 2013 to 2020. The potential net savings in avoided CHD-related hospital utilization costs after accounting for the cost of omega-3 dietary supplements at preventive daily intake levels would be more than $3.88 billion in cumulative health care cost savings from 2013 to 2020.
  • the use of folic acid, B6, and B12 among the target population at preventive intake levels could yield avoided CHD-related hospital utilization costs savings of an average savings of $1.52 billion per year from 2013 to 2020. The potential net savings in avoided CHD-related health care costs after accounting for the cost of folic acid, B6, and B12 utilization at preventive daily intake levels would be more than $5.23 billion in cumulative health care cost net savings during the same period.

The authors conclude that targeted dietary supplement regimens are recommended as a means to help control rising societal health care costs, and as a means for high-risk individuals to minimize the chance of having to deal with potentially costly events and to invest in increased quality of life.

These conclusions read like a ‘carte blanche’ for marketing all sorts of useless supplements to gullible consumers. I think we should take them with more than a pinch of salt.

To generate results of this nature, it is necessary to make a number of assumptions. If the assumptions are wrong, so will be the results. Furthermore, we should consider that the choice of supplements included was extremely limited and highly selected. Finally, we need to stress that the analysis related to a very specific patient group and not to the population at large. In view of these facts, caution might be advised in taking this analysis as being generalizable.

Because of these caveats, my conclusion would have been quite different: provided that the assumptions underlying these analyses are correct, the use of a small selection of dietary supplements by patients at risk of CHD might reduce health care cost.

The fish oil (FO) story began when a young Danish doctor noticed that there were no heart attacks in Greenland. Large epidemiological studies were initiated, mechanistic investigations followed, and a huge amount of fascinating data emerged. Today, we know more about FO than most other dietary supplements.

Fish oil contains large amounts of omega-3 fatty acids which are thought to be beneficial in treating hypertriglyceridemia,  preventing heart disease.  In addition, FO is often recommended for a wide variety of other conditions, such as  cancer, depression, and macular degeneration. Perhaps the most compelling evidence exists in the realm of inflammatory diseases; the mechanism of action of FO is well-studied and includes powerful anti-inflammatory properties.

Australian rheumatologists just published a study of FO supplements for patients suffering from rheumatoid arthritis (RA). Specifically, they examined  the effects of high versus low dose FO in early RA employing a ‘treat-to-target’ protocol of combination disease-modifying anti-rheumatic drugs (DMARDs).

Patients with chronic RA <12 months’ who were DMARD-naïve were enrolled and randomised 2:1 to FO at a high dose or plaacebo (low dose FO for masking). These groups were given 5.5 or 0.4 g/day, respectively, of  eicosapentaenoic acid + docosahexaenoic acid. All patients received methotrexate (MTX), sulphasalazine and hydroxychloroquine, and DMARD doses were adjusted according to an algorithm taking disease activity and toxicity into account. DAS28-erythrocyte sedimentation rate, modified Health Assessment Questionnaire (mHAQ) and remission were assessed three monthly. The primary outcome measure was failure of triple DMARD therapy.

The results indicate that, the FO group, failure of triple DMARD therapy was lower (HR=0.28 (95% CI 0.12 to 0.63; p=0.002) unadjusted and 0.24 (95% CI 0.10 to 0.54; p=0.0006) following adjustment for smoking history, shared epitope and baseline anti–cyclic citrullinated peptide. The rate of first American College of Rheumatology (ACR) remission was significantly greater in the FO compared with the control group (HRs=2.17 (95% CI 1.07 to 4.42; p=0.03) unadjusted and 2.09 (95% CI 1.02 to 4.30; p=0.04) adjusted). There were no differences between groups in MTX dose, DAS28 or mHAQ scores, or adverse events.

The authors conclude that FO was associated with benefits additional to those achieved by combination ‘treat-to-target’ DMARDs with similar MTX use. These included reduced triple DMARD failure and a higher rate of ACR remission.

These findings are most encouraging, particularly as they collaborate those of systematic reviews which concluded that evidence is seen for a fairly consistent, but modest, benefit of marine n-3 PUFAs on joint swelling and pain, duration of morning stiffness, global assessments of pain and disease activity, and use of non-steroidal anti-inflammatory drugs and …there is evidence from 6 of 14 randomized controlled trials supporting a favourable effect of n-3 LCP supplementation in decreasing joint inflammation in RA. And you don’t need to buy the supplements either; regularly eating lots of fatty fish like mackerel, sardine or salmon has the same effects.

So, here we have an alternative, ‘natural’, dietary supplement or diet that is supported by reasonably sound evidence for efficacy, that has very few adverse effects (the main one being contamination of the supplement with toxins), that generates a host of potentially useful effects on other organ systems, that is affordable, that has a plausible mechanism of action…. Hold on, I hear some people interrupting me, FO is not an alternative medicine, it is mainstream! Exactly, an alternative medicine that works is called….MEDICINE.

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