Tag Archives: cancer

Naked Mole Rat: Freak of Nature

A frequent entry in ‘Top 10 Ugliest Animal’ lists, the naked mole rat truly is a sight to behold. A cross between, a mole and a rat, with a sprinkle of naked has produced a physical abomination. Despite its looks, the naked mole rat has remarkable physiology and is one of the most interesting animals, biologically speaking, ever discovered.

From insensitivity to pain, to powerful cancer resistance, the naked mole rat has intrigued scientists the world over for attributes not found in other mammals. Studying the perplexing physiology of these animals may unlock new therapeutic avenues for the treatment of human disease, cancer being the most relevant.

The naked mole rat is a burrowing animal and described as ‘eusocial’  – this is considered the highest level of organisation in animal society and involves things like co-operative brood care (all mothers looking after all infants collectively) and organised division of labour. Hive animals such as ants and termites are considered eusocial but only two known eusocial mammals have been reported, including the naked mole rat.

The naked mole rat lives in unusually harsh conditions which is thought to be the main driving force behind their strange physiological adaptions. They live primarily in arid African deserts . Groups of about 80 individuals reside in complex underground burrow systems. Like hive insects, naked mole rats have a ‘queen’  female who produces young which are tended to by non-breeding females. ‘Worker’ animals serve to defend the hive from attack, acquire food and maintain/dig the tunnel systems. It’s all pretty mad that this set-up exists in a mammal as this sort of system is very much associated with insects.

However, their social layout is just the tip of the iceberg when it comes to these remarkable creatures. Lets take a look at why the naked mole rat is a ‘medical marvel’.

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#1 Pain Insensitivity

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This can be explained, from a biological standpoint, rather simply. We know that naked mole rats lack a key neurotransmitter in the skin called Substance P which in ‘normal’ mammals is very important in transmitting pain signals to the central nervous system (1).

In an interesting experiment, it was shown that if Substance P is injected into the naked mole rats, they once again feel pain but NOT to acids. So the system to feel pain in the skin exists but they have evolved to lack a key component and also cannot feel acid-induced pain even when this key component is reintroduced (2). So we know why, on a cellular level they don’t feel pain but what about why this evolved in the first place?

Due to where they live the leading theory is that this lack of substance P is to combat pain from acid build up in tissues which results from living in cramped poorly oxygenated spaces with high levels of carbon dioxide.

They have other adaptions which fit with this low oxygen environment including possessing blood with an extremely high affinity for oxygen as well as a very low respiratory and metabolic rates. They consume a fraction of the energy of a similarly sized rat (3).

Crazy stuff and a remarkably specific adaption to the environment.


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#2 Resistance To Cancer

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Naked mole rats are highly resistant to tumours (4) but can still suffer from related disorders – in 2016 two individuals born and raised in captivity were shown to have developed tumours for the first time, so it is possible. Bear in mind, these animals are living in a much more oxygen rich environment that they do in the wild which may have promoted tumour growth (5).

Studies have revealed the exact cellular mechanisms by which naked mole rats are resistance to cancers. Whereas most mammals, including us, have one major genetic defence against tumours, naked mole rats possess two.

Gene p 27 is an ‘over-crowding gene’ that prevents cell division once individual cells make contact with one another. This is known as contact inhibition. We all posses this gene.  Another similar gene called p 16 which functions in a similar manner is used by naked mole rats alongside p 27 acting as a double barrier to uncontrolled cellular proliferation. If their version of p 27 is mutated and ceases to function, p 16 can fulfil this role alone (6). We however are not so lucky.

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What even is this?

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More recent evidence suggests that the naked mole rats produce a unique version of a compound that we mammals share but which acts as a kind of anti-cancer agent (7). Surprisingly the same compound which gives them stretchy skin may also be why they are so cancer resistance. Hyaluronan is a component of connective tissue found across all mammals. Naked mole rats have a particularly long version of this molecule. Removing this molecule from cultured mole rat cells increases cancer rates massively. This compound is thought to be key in why naked mole rat cells have much more sensitive cellular  contact inhibition in comparison to humans

Work is currently being undertaken to work out how we would potentially apply this to human cancer treatments.

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#3 Thermoregulation

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Another bizarre trait. Naked mole rats do not regulate their body temperature like other mammals.  They are described as ‘thermoconformers’ whereas mammals in general are ‘thermoregualtors’ (8) . Most mammals maintain a constant internal body temperature regardless of ambient temperature. However, naked mole rats body temperature tracks ambient temperature, more like a reptile. Naked mole rats have been shown to make great use of behavioural thermoregulation.

When cold, they huddle together in shallower parts of their tunnels to absorb heat from the sun, when too warm, they retreat to deeper and cooler parts of their homes (9).

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#4 Long Life Span

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Not only do naked mole rats not get cancer and not feel pain but they also live for bloody ages, You guessed it. They are hell spawn.

For their size they live for absolutely ages – up to 31 years (!). The general rule of thumb is the smaller the animal the shorter the life span. Not true of the mole rat. Naked mole rats live up to 10 times longer than a rat (and at 3 years, that rat would be ancient). The exact reasons for why they live so long aren’t fully understood but a number of plausible physiological adaptions may explain it.

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  • As already discussed, they are highly resistance to cancer, something which plagues male rats (10)

 

  • They maintain healthy vascular function well into their old age and do so much better than other rodents (11)

 

  • They can reduce metabolic rate during hard times which may help them avoid age-induced damage from oxidative stress (12)

 

  • DNA repair pathway genes expressed much more highly then short lived rodents: better DNA repair may facilitate greater longevity and does fit with the well known ‘DNA damage theory of aging’ (13,14)

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True freaks of nature but ones which hold therapeutically valuable information regarding cellular mechanisms of cancer resistance. Don’t judge a book by its cover. Naked mole rats are ugly bastards but one day you may owe your life to research successfully carried out on these little ball bags.

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As always, thanks for stopping by,

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-ScienceGuy

The Slap Therapy Tragedy

The ‘Slap Therapy’ Tragedy

 

I’ve decided to write a quick post regarding a couple of truly disturbing news stories I’ve read recently.

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The topic?

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Slapping people (including infants) to cure their diseases and illnesses…

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These sort of stories are important because they highlight pretty much everything I stand against and one of the main reasons for this websites existence. That is, charlatans taking advantage of people who don’t know better.

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In these cases, deaths have occurred due to the irresponsible and reckless behaviour from practitioners of something called ‘slap therapy’.

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Here is a link to the official website – almost everything on here, to me, is preposterous.

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Claims include that slap therapy is:

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‘Superior to modern medical practices’

‘Effective on almost all diseases’

The testimonials are even worse:

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‘A Self-healed Story of an Advanced Prostate Cancer Patient’ – If your advanced cancer has self-resolved, this is very rare and you are extremely lucky. However looking more closely, this isn’t a self healed story. The actual testimonial states that the tumour has reduced in size. This can occur for a number of reasons and is not sufficient evidence to claim a cancer is ‘healed’. 

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‘Bladder Cancer Self Healed’ – By their own admission they went through intensive radiotherapy treatment for the cancer before starting slap therapy. 

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‘Food Poisoning Self-Healed with Paida’ – Food poisoning is usually a short self-resolving affliction lasting no more than one or two days. The account says that immediately after eating a peach a man fell ill with food poisoning – illness does not occur immediately after consumption of contaminated food. This account is likely false.

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‘How Did I Self-Heal My Type 1 Diabetes?’ – This account is scary as it echoes events that led to the death of a young diabetic boy (detailed further below). A type 1 diabetic woman, under advice from a man with no medical background or training and a severely warped understanding of human biology, massively reduced her insulin intake. However on further inspection she is still receiving insulin on a  daily basis, just less than previously. This is no ‘healing’ type 1 diabetes – a huge amounts of research is focused on combating beta cell loss in type 1 diabetics. This isn’t something that spontaneously reverses or can be fixed due to being slapped. Likely, this woman can function normally on the amount of insulin she is receiving. Nevertheless she is putting her health at risk. 

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Well that’s me sold! Sign me up. Except don’t.

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This isn’t harmless homeopathy, this is physically beating the ‘toxins’ out of someone. Practitioners claim that all the serious bruising from the slapping aren’t bruises but actually harmful toxins leaving the body.

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This has directly led to the death of one elderly diabetic women after a number of people tried to beat the diabetes out of her. The news report suggest the woman had a life long phobia of needles. Having to inject insulin was therefore extremely difficult for her and she had frequently sort alternative therapies. These slap therapists preyed directly on this fear and its resulted in this poor woman’s death.

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An excerpt from the news story from the woman’s son…

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Carr-Gomm’s son Matthew, 43, said his mother, from Lewes, East Sussex, had been given false hope.

“I am certain that if she hadn’t gone on this course, she would still be alive today. She was convinced this alternative treatment was going to have a positive effect,” he said.

“She had a lifelong fear of needles, so diabetes was probably the worst illness she could get. That was why she was so keen to try alternative therapies.”

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But the story goes even further and becomes even more tragic.

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A 7 year old boy has also died as a direct or in-direct result of this therapy. The boy, a type 1 diabetic, died during a week long slap therapy retreat (at a cost of 1800 USD – far from cheap). The boy fell ill and began to vomit mid-way thought the retreat. He died on the way to hospital. Investigations are trying to determine whether he was taken off his insulin during the retreat – if so what were the parents doing agreeing to something so foolish!. Either way a young boy has lost his life.

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Parents convinced that slap therapy is the key to healing have started slapping the shit out of their babies and children as well. I really don’t know what to say about this. It’s so far into ‘lunatic’ territory that it boggles the mind. The investigation contains some fairly disturbing videos. And remember, these are the kids parents doing this. Not some stranger. They truly believe this anti-science alternative, dangerous ‘therapy’.

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In a world where the alternative therapy market continues to grow year on year into a mammoth industry, it’s so important that we make a stand and demand evidence and accountability for people who sell and promote this garbage. Selling therapies that simply don’t work is one thing – asking someone to beat their kid because it will cure their diabetes is an entirely different matter and should result in prison time for the charlatan in question. Holding the parents accountable is a tricky one and perhaps best left for a discussion in the comments.

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Thanks for reading,

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-ScienceGuy

 

The truth about Fish Oil

Many cupboards across the country are home to a little tub of those squishy yellow fish oil pills.

Over the last decade or so, fish oil capsules have become exceptionally popular and now take pride of place on any health supplement shop shelf.

Eating fish is  generally considered healthy. Fish, in general, is low in saturated fats and less calorific than red meats. Populations that consume large amounts of fish also have lower incidence of heart disease. Additionally, high consumption of red meat has been linked with increased risk of bowel cancer (1) – further promoting the eating of fish is therefore good for public health.

The idea for a long time has been that the oils and fats in fish is what really sets it apart from other meat products – hence why we now see fish oil supplements.

But what is the truth about eating fish oils regularly? Will you really be ‘healthier’? Are fish oils protective against heart disease for example?

Lets find out…but first a bit of background about what fish oils actually are.

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What are ‘Fish Oils’?

 

Fish oil is simply an oily substance derived from the tissues of ‘oily’ fish. The most oily fish are sardines, mackerel, salmon, halibut and tuna. Lots of other fish also contain these oils but to a lesser degree (2).

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 The major components of fish oil are the omega-3 fatty acids:

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Eicosapentaenoic acid (EPA)

Docosahexaenoic acid (DHA)

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An additional type of fatty acid is also important in human health but found in nuts, not oily fish:

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α-linolenic acid (ALA)

.Both EPA and DHA are described as ‘essential’ – we have to obtain these fatty acids from our diets, we cannot make them ourselves (3). ‘Fatty’ fish such as salmon and sardines are great sources of both of these compounds. If you aren’t a fan of fish, flax seeds, pumpkin seeds and walnuts are just a few other dietary sources from which you can obtain high levels of EPA and DHA.

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A handy conversion schematic from Dr. Ben King at drbenking.com

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Omega-3 fatty acids are important for normal metabolic function and are especially important for growth in infants (4). DHA is found in large quantities in the brain where it acts as a major structural component (5).  Aside from structural function, DHA and EPA are thought to play an important role in brain health – good evidence suggest omega-3s are important in maintaining mood stability and show potential in combating depression (discussed more below).

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As with a lot of popular supplements – many remarkable health benefits have been attributed to omega-3s and the broader term of ‘fish oils’. As always, as I have shown you before, when we dig deeper we see that many common claims about supplements either exaggerate the truth or are entirely made up. Some supplements have very weak literature and research behind them, fish oils however have been researched in depth for a number of years so we can draw firmer conclusions regarding their therapeutic efficacy.

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Are there health benefits: What does the science say?

 

At some point or another, fish oils have been said to cure or alleviate an extremely wide range of maladies and diseases. I won’t cover them all here as the list is practically endless and mostly made up. Instead I will focus on common diseases and pathologies which have the most research behind them concerning fish oils as a therapeutic supplements.

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.Cardiovascular Disease

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CVD and fish oils go hand in hand. Aside from widely cited ‘mental boosting’ effects, the next benefit on the list of fish oil supplements is almost almost cardiovascular health. We know that dietary fat intake is very important for cardiovascular health and can be a major indicator of risk of heart attack. In general, we know that trans fats are especially bad when it comes to heart health and that polyunsaturated fats are a much better choice and may even be protective against heart disease if eaten in moderation (6). It therefore makes sense that so much research has investigated the effects of omega-3 fatty acids and CV health and disease risk.

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Basic anatomy of the heart – many of these components can be adversely affected by cardiovascular disease

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Most of that research sends a clear message: Fish oil supplements do not protect against heart attacks of strokes. Although some individual papers have shown potential benefit – i.e. two papers from 1999 and 2009 (7,8) suggesting fish oils may have beneficial effects on certain abnormal heart rhythms. However, since then meta studies have refuted that specific claim (9) and also gone on to conclude that…

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”Omega-3 Fatty Acid supplementation did not reduce the chance of death, cardiac death, heart attack or stroke”

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This is the conclusion of a 2012 meta-study (Journal of the American Medical Association) which analysed the data from 20 separate studies and well over 60,000 patients (10). This is a good amount of data so we can be confident in this conclusion as it stands.

It is important to note that although fish oil doesn’t seem to prevent death from heart attacks of stroke it does appear to have beneficial effects for previous sufferers of heart attacks and other people with a history of cardiovascular disease. Omega-3s possess modest anti-inflammatory properties (11) and it is probably because of this that a cohort of heart attack survivors that received daily fish oil supplements for 6 months showed improved heart function overall and lower markers of systemic inflammation than their control counterparts (12). Furthermore, omega-3 fatty acid supplementation greater than one gram a day for at least a year may be protective against cardiac death, sudden death, and myocardial infarction in people who have a history of cardiovascular disease.

Another meta study also concluded that there was ‘tentative’ evidence of an anti-inflammatory effect  from fish oil supplementation. More data will be needed to take a stronger position on this in the future.

Although not directly heart protective in healthy individuals the current evidence suggests fish oil supplements may benefit those who have a history of heart disease and/or have suffered a heart attack.

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Prostate Cancer

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I’ve decided to mainly write about prostate cancer here as this is the type of cancer with the most relevant studies. Omega-3s are often touted as having a strong anti-cancer effect but as I have said before: Just because a compound kills or inhibits the growth of cancer cells in vitro (in a cell culture dish) does not mean it qualifies as a cancer therapy by itself.

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More true advice has never been given

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Some studies have shown that fish oils rich in Omega-3s do inhibit tumour cell growth in vitro. This effect was deemed strong enough to suggest that a diet rich in Omega-3 fatty acids be used alongside traditional breast cancer treatments (13) – this may actually prove beneficial (this does not endorse Omega-3 fatty acids as a treatment by itself in any way).

But what about studies where they gave actual patients with cancer Omega-3 supplements or looked directly at Omega-3 blood concentrations? This has been mostly done with prostate cancer patients.

The area remains controversial due to the publication of a few papers with conflicting results.

One paper demonstrated that increased DHA in the blood was associated with a reduction in prostate cancer risk (14). However, two other papers have shown almost the exact opposite. One group showed that increased levels of DHA and EPA was associated with an increased risk of more aggressive prostate cancer (15).  Another group presented evidence that suggested a link between high blood levels of omega -3 fatty acids and an increased risk of prostate cancer (16).

These papers have all been published in the last few years, starting in 2012, so this is a an actively contested research  topic that has yet to see a solid consensus emerge. As such we can say that overall, given the available data, the effects of omega-3 supplementation on cancer, including prostate cancer, is currently inconclusive. 

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Alzheimer’s Disease

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It is unlikely that dietary intervention will prevent Alzheimer’s and even more unlikely that symptoms will be reversed once they manifest. A 2012 Cochrane meta-analysis (17) pooled the data from studies when individuals over the age of 60 had been given fish oils as a supplement. They found that taking fish oil supplements did not provide protection against the development of Alzheimer’s in the over 60s.

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In their words…

“Our analysis suggests that there is currently no evidence that omega-3 fatty acid supplements provide a benefit for memory or concentration in later life”.

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It is important to note that this meta-study specifically looked at those over the age of 60 as Alzheimer’s is typically a disease of old age. This study is therefore limited in a number of ways. It cannot tell us whether fish oil supplementation in younger years may ultimately prove protective against Alzheimer’s in old age. Although this remains unlikely, fatty acids are important brain components and do play a role in mood and brain function so there may be an as of yet, undiscovered link.

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Mental Health

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Overall, studies and meta-studies in this area have expressed the need for many more randomised controlled studies in order to increase the data pool and that the data is, in general, limited. The major review that suggested this need for more data also showed that omega-3s were an effective adjunctive therapy for depressive (but not manic) symptoms in bipolar disorder (18).

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The most recent meta-study in this area from 2014, an analysis of 11 studies, looked at treating depression in patients diagnosed with Major Depressive Disorder (MDD) and those with depression but without a diagnosis of MDD.

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They concluded…

‘The use of omega-3 PUFA is effective in patients with diagnosis of MDD and on depressive patients without diagnosis of MDD.”

Omega 3 fish oil supplements appear to be effective in treating depression. More data more establish this more strongly in the future.

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Hypertension (High Blood Pressure)

Omega-3s may have a small beneficial effect on hypertension by lowering blood pressure (19). The effect currently shown in studies is small and appears to only effect individuals with hypertension. Studies which failed to replicate the blood pressure reduction may be due to dosage issues. Additionally, DHA and EPA don’t seem to have the same efficacy with DHA having potentially greater effects.

This area is worth exploring in greater detail with more data before a solid conclusion can be drawn.

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Are there any dangers associated with fish oil supplements?

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A 2013 review on fish oil supplement dangers concluded…

”appear mild at worst and are unlikely to be of clinical significance”

This is true of eating fish in general…not just taking fish oil supplements.

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Mercury

Heavy metal accumulation can be a problem with fish and predatory fish at the top of the food chain have higher levels of mercury due  to bio-accumulation over time. Mercury levels can range from very low to worryingly high in a single serving of fish. Usually from 10 ppb (parts per billion) of mercury all the way up to 1,000 (20). Luckily your average fish oil supplement contains 2 ppb mercury- well within tolerable limits (21).

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The process of bio-accumulation means large predatory fish have greater levels of environmental toxins in their system than smaller prey fish. Original image from jessbanda.wordpress.com

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Dioxins and dioxin like chemicals

Chronic exposure to low levels of dioxins may be carcinogenic and the chemical is classified as a human carcinogen (22).  There is also evidence that uterine exposure to dioxins leads to subtle developmental issues in children. In a similar fashion to mercury, chemicals like dioxin bio accumulate in fish so that the concentrations in the fish are much greater than the surrounding environment. In reputable brands of  fish oil supplements, dioxins will not be found. Always buy your supplements from reputable brands and suppliers.

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Vitamin A

The liver and liver products of fish (i.e. cod liver oil) contain omega-3, but also the active form of vitamin A.

High intake of vitamin A can lead to dangerous Hypervitaminosis A.

I have covered the role of vitamins in health extensively here.

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% Recommended Daily Allowances

FDA guidelines state that it is  safe to take up to 3000 mg of omega-3 per day. However, that is pure omega-3 oil not 3000 mg of fish oil.

Fish oil contain varying levels of omega-3 which should be labelled clearly on the back of the packaging.

A typical 1000 mg fish oil pill contains about 200-400 mg of omega-3 fatty acids. You would have to take over ten pills a day to be over recommended allowances – no chance of that.

.Ultimately taking fish oil supplements from a reputable producer and seller is no more dangerous than consuming fish frequently.

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The Final Word

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Dissecting out exactly what certain molecules and compounds are doing in the body is always tricky. This is certainly true of supplements. There is no doubt that supplements are a great idea for those deficient in a particular nutrient but the benefits of taking more of a particular nutrient when you are already meeting requirements are much harder to determine. This is a common theme running through supplement use in general.

Overall fish oils (Omega-3s) are physiologically important and play a number of key roles in the body. The science suggests that  supplementing with fish oils is no where near as ‘powerful’ as some manufactures would have you believe…

Currently the data suggests there is no clear protective effect against…

Risk of cancer

Risk of stroke

Risk of heart attack

Development of Alzheimer’s Disease

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However! There is some evidence that Omega-3s are effective in…

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Treating certain types or depression – more data would be ideal

Increasing general heart function following a heart attack

General reduction in markers of  systemic inflammation

May have small beneficial effects on hypertension

Although there are some minor risk associated with high fish oil intake (potential heavy metal ingestion), this risk is no greater than when simply eating fish. On this topic, researchers at Harvard’s School of Public Health said…

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 ”The benefits of fish intake generally far outweigh the potential risks.”

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I myself really enjoy eating fish – mainly salmon and tuna. I also eat mixed nuts frequently which include walnuts. All good sources of Omega-3 fatty acids. I also always have a tub of fish oil capsules handy at home. I do not take them every day but if I haven’t got hold of fresh fish for a week or two I will go ahead and supplement for a few days with capsules.

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If you fancy doing the same, grab them for cheap down below. Also, check out the Microalgae Capsules – the vegetarian alternative to fish oil capsules.

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Thanks for reading!

-ScienceGuy

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References

 

  1. Zhu, H; et al. (2013). “Red and processed meat intake is associated with higher gastric cancer risk: a meta-analysis of epidemiological observational studies.”. PLOS ONE. 8 (8)
  2. Kris-Etherton, Penny M.; William S. Harris, Lawrence J. Appel (2002). “Fish Consumption, Fish Oil, Omega-3 Fatty Acids, and Cardiovascular Disease”. Circulation. 106 (21): 2747–57.
  3. Moghadasian, Mohammed H. (2008). “Advances in Dietary Enrichment with N-3 Fatty Acids”. Critical Reviews in Food Science and Nutrition. 48 (5): 402–10.
  4. Freemantle E, Vandal M, Tremblay-Mercier J, Tremblay S, Blachère JC, Bégin ME, Brenna JT, Windust A, Cunnane SC (2006). “Omega-3 fatty acids, energy substrates, and brain function during aging”. Prostaglandins, Leukotrienes and Essential Fatty Acids. 75 (3): 213–20.
  5. “Nutrition for the Brain” (PDF)/DHA in Brain and Retina Structure” (PDF)
  6. Zaloga GP, Harvey KA, Stillwell W, Siddiqui R (2006). “Trans Fatty Acids and Coronary Heart Disease”. Nutrition in Clinical Practice. 21 (5): 505–512.
  7. Charnock John S (1999). “The role of omega-3 polyunsaturated fatty acid-enriched diets in the prevention of ventricular fibrillation” Asia Pacific Journal of Clinical Nutrition. 8 (3): 226–30.
  8. Li GR, Sun HY, Zhang XH, Cheng LC, Chiu SW, Tse HF, Lau CP (2009). “Omega-3 polyunsaturated fatty acids inhibit transient outward and ultra-rapid delayed rectifier K+currents and Na+current in human atrial myocytes”. Cardiovasc Res. 81 (2): 286–93.
  9. Khawaja, Owais; Gaziano, J. Michael; Djoussé, Luc (2012-02-01). “A meta-analysis of omega-3 fatty acids and incidence of atrial fibrillation”. Journal of the American College of Nutrition. 31 (1): 4–13.
  10. Rizos, E. C.; Ntzani, E. E.; Bika, E; Kostapanos, MS; Elisaf, MS (2012). “Association Between Omega-3 Fatty Acid Supplementation and Risk of Major Cardiovascular Disease Events: A Systematic Review and Meta-analysis”. Journal of the American Medical Association. 308 (10): 1024–33.
  11. Wall R, Ross RP, Fitzgerald GF, Stanton C (2010). “Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids”. Nutr Rev. 68 (5): 280–89.
  12. Heydari B, Abdullah S (2016) Effect of Omega-3 Acid Ethyl Esters on Left Ventricular Remodelling After Acute Myocardial Infarction: The OMEGA-REMODEL Randomised Clinical TrialCirculation2;134(5):378
  13. Jiajie Liu and David W. L. Ma (2014).’‘The Role of n-3 Polyunsaturated Fatty Acids in the Prevention and Treatment of Breast Cancer” Nutrients. 6(11): 5184–5223.
  14. Heinze, VM; Actis, AB (February 2012). “Dietary conjugated linoleic acid and long-chain n-3 fatty acids in mammary and prostate cancer protection: a review”. International journal of food sciences and nutrition. 63 (1): 66–78.
  15. Chua ME, Sio MC, Sorongon MC, Morales ML (May–June 2013). “The relevance of serum levels of long chain omega-3 polyunsaturated fatty acids and prostate cancer risk: a meta-analysis”. Canadian Urological Association Journal. 7 (5–6): E333–43.
  16. Brasky TM, Darke AK, Song X, et al. (August 2013). “Plasma phospholipid fatty acids and prostate cancer risk in the SELECT trial”. J. Natl. Cancer Inst. 105 (15): 1132–41.
  17. Sydenham E, Dangour A, Lim W (2012) ”Omega 3 fatty acid for the prevention of cognitive decline and dementia” Cochrane Database of Systematic Reviews
  18. Grosso, G.; Pajak, A.; Marventano, S.; Castellano, S.; Galvano, F.; Bucolo, C.; Caraci, F. (2014). “Role of Omega-3 Fatty Acids in the Treatment of Depressive Disorders: A Comprehensive Meta-Analysis of Randomized Clinical Trials”. PLoS ONE. 9 (5)
  19. Miller PE, Van Elswyk M, Alexander DD (July 2014). “Long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and blood pressure: a meta-analysis of randomized controlled trials”. American Journal of Hypertension. 27 (7): 885–96
  20. Mercury Levels in Commercial Fish and Shellfish (1990–2010) U.S. Food and Drug Administration. Accessed 14 January 2017
  21. Top 10 Fish Oil Supplements – LabDoor”. LabDoor. Accessed  14 January 2017
  22. Steenland K, Bertazzi P. (2004) ‘‘Dioxin Revisited: Developments Since the 1997 IARC Classification of Dioxin as a Human Carcinogen”. Environmental Health Perspectives. 112 (13) 1265-1268