Fish Oil Fables
Even though people like to blame sugar for blood sugar issues, and many say fish oil is a miracle cure for diabetes (and numerous other inflammatory conditions), lots of science has demonstrated why the opposite is true, in both cases.
“The PUFA [polyunsaturated fatty acid] diet contained a high proportion of n-3 fatty acids…Average blood glucose concentrations during the third week were significantly higher…on PUFA than on the saturated fat diet…” (Vessby B, et al., 1992)
“…effects of…fish-oil supplementation (6 g/d) on…plasma glucose disappearance (Rd glucose)…Fish oil…reduced glucose metabolic clearance rate…Carbohydrate oxidation tended to be less stimulated…Lipid oxidation tended to be more stimulated…fish oil reduced the rate of plasma glucose disappearance by 26% by reducing glucose metabolic clearance rate…” (Delarue J, et al., 2003)
“…dietary fish oil supplementation adversely affected glycemic control in NIDDM [non-insulin-dependent diabetes mellitus] subjects…The effect of safflower oil supplementation was not significantly different from fish oil…fish oil supplementation should be used with caution…” (Mark Borkman, et al., 1989)
It is a popularly held belief (based on scant biological evidence), that fish oil and other polyunsaturated fats (PUFAs), make up an important part of a healthy diet, that they can be safely used for protection against inflammatory illness, and that not getting enough can eventually lead to what is often referred to as an ‘essential fatty acid deficiency.’
Rather than being harmful however, avoiding exposure to the omega-3 (and omega-6) PUFAs, has been shown to promote increased glucose uptake, and help improve overall metabolic function.
“After omega-3 fatty acid withdrawal, fasting glucose returned to baseline. Omega-3 fatty acid treatment in type II diabetes leads to rapid but reversible metabolic deterioration, with elevated basal hepatic glucose output and impaired insulin secretion…Caution should be used when recommending omega-3 fatty acids in type II diabetic persons.” (Glauber H, et al., 1988)
Evidence suggests that under these kinds of conditions, where PUFAs circulation is reduced, and metabolism is allowed to work more effectively, a reasonably high sucrose diet (combined with protein and other important nutrients), can help protect against stress and inflammation, and can improve blood sugar regulation issues and other symptoms related to diabetes. Sucrose and fructose have been used as a treatment for diabetes.
“Dietary intakes of total carbohydrates, starch, sucrose, lactose or maltose were not significantly related to diabetes risk after adjustment for confounders…in the residual method for energy adjustment, intakes of fructose and glucose were inversely related to diabetes risk.” (Ahmadi-Abhari S, et al., 2014)
“Replacement of either glucose or sucrose by fructose resulted in significantly lowered peak postprandial blood glucose, particularly in people with prediabetes and type 1 and type 2 diabetes. Similar results were obtained for insulin…Peak postprandial blood triglyceride concentrations did not significantly increase.” (Evans RA, et al., 2017)
“…fructose administered with glucose decreases the glycemic response to a glucose load, especially in those with the poorest glucose tolerance…Low-dose fructose improves the glycemic response to an oral glucose load in adults with type 2 diabetes…” (Moore MC, et al., 2001)
Polyunsaturated fats (PUFAs) coming from fish oils, quickly and easily break down (due to lipid peroxidation), into a variety of highly reactive chemicals which have very harmful and inflammatory effects, interfering with metabolism and preventing cells from being able to effectively use glucose for fuel.
The breakdown products of fish oil (and other PUFAs) include substances like acrolein, malondialdehyde, 4-hydroxy-2-hexenal, 4-hydroxy-2-nonenal, and crotonaldehyde.
“Marine lipids contain a high proportion of polyunsaturated fatty acids (PUFA), including the characteristic long chain (LC) n-3 PUFA. Upon peroxidation these lipids generate reactive products, such as malondialdehyde (MDA), 4-hydroxy-2-hexenal (HHE) and 4-hydroxy-2-nonenal (HNE), which can form covalent adducts with biomolecules and thus are regarded as genotoxic and cytotoxic. PUFA peroxidation can occur both before and after ingestion.” (Larsson K, et al., 2016)
The fish oils have been shown to be able to speedily suppress immune function, often resulting in a temporary reduction in existing processes of inflammation. This can give the illusory appearance of improvement, because of immediate but short term symptom reduction.
In the longer term, the immunomodulatory stress promoting impact of these so called ‘anti-inflammatory’ fats, have many anti-metabolic effects, such as worsening blood sugar dysregulation issues (and other diabetes related symptoms), as well as increasing the likelihood of degenerative and inflammatory conditions, including cancer and Alzheimer’s disease.
“…consistent evidence for immunomodulatory effects of dietary ω-3 PUFA (EPA + DHA) intakes. High LCω-3PUFA consumption may alter the immune response to microbes in the gut, alter the community structure of the microbiota and enhance susceptibility to IBD and infection-induced inflammation and cancer.” (Fenton JI, et al., 2013)
“…long-term intake of limited amounts of oxidized n-3 PUFA…enhances markers of oxidative stress and inflammation…partly due to intestinal absorption of 4-HHE…high DHA supplementation…causes a significant increase in plasma levels of 4-HHE…the oxidized n-3 PUFA diet induced higher IL-6, MCP-1 in plasma, and activation of transcription factor NF-κB…implicated in…inflammation…altogether our results suggest a link between oxidized n-3 PUFA and metabolic inflammation…” (Manar Awada, et al., 2012)
Fish oil consumption has been shown to promote the release of the inflammatory stress substance nitric oxide, and there are studies which have attempted to frame this as something which is beneficial for metabolic health.
But it’s almost always possible to interpret the physiological responses to stress as being something good, and misinterpretations get reinforced by short term suppression of symptoms. This is common with regards to nitric oxide, due in part to its protective role in relation to local and acute issues.
“Dietary supplementation with fish oils has been shown to augment endothelium-dependent relaxations, principally by improving the release of nitric oxide from injured endothelium…” (McVeigh GE, et al., 1993)
“We investigated the effects of EPA [eicosapentaenoic acid…omega 3] and elevated glucose on NO production by human endothelial cells…EPA…significantly enhanced [NO2] production…EPA-E decreased the glucose-mediated inhibition of NO production…” (Okuda Y, et al., 1997)
“…we investigated the effects of two different types of natural fish oils containing different amounts of the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)…the stabilized DHA-rich oil increased the brain NOS activity (+33%, P < 0.01).” (Engström K, et al., 2009)
Regarding the long term, however, there are many studies which show, that systemic increases in nitric oxide promote disease, including diabetes, Alzheimer’s, and cancer, and numerous other inflammatory conditions. Just because we have mechanisms available to us which protect against stress, does not mean that using a substance like fish oil (that can trigger a stress response and cause what looks like an improvement in the short term), is doing good things for the overall function of metabolism.
Acrolein, a major breakdown product of fish oil and other omega-3 fats, has been shown to promote nitric oxide. Rising levels of acrolein are associated with the progression of the diseases of inflammation, contradicting studies which argue that the consumption of fish oil is protective.
“ACR [acrolein] could stimulate iNOS [inducible nitric oxide synthase] and COX-1/COX-2, producing lymphocyte migration and increases of NO [nitric oxide] and PGs [prostaglandins].” (Linares-Fernández B, Alfieri AB., 2009)
“Lipid peroxidation leads to the formation of a number of aldehydes by-products, including malondialdehyde (MDA), 4-hydroxy-2-nonenal (HNE), and acrolein…acrolein is the most reactive…In brain from patients with AD [Alzheimer’s disease], acrolein has been found to be elevated in hippocampus and temporal cortex where oxidative stress is high. Due to its high reactivity, acrolein is not only a marker of lipid peroxidation but also an initiator of oxidative stress…” (Singh M, et al., 2010)
“…results showed that α-linolenic acid, an omega-3 fatty acid, generated more acrolein and crotonaldehyde than did linoleic acid, an omega-6 fatty acid…Omega-3 fatty acids might be easily degraded to smaller monoaldehydes or dicarbonyls…Omega-3 fatty acids have been considered as health improvement components for a long time. However, on the basis of the results presented here, use of omega-3 fatty acids should be re-evaluated in vivo for safety purposes.” (Wang Y, Cui P., 2015)
Acrolein has also been shown to promote the release of serotonin, and serotonin (much like nitric oxide), is an inflammatory stress substance, that directly interferes with the function of energy metabolism. In fact nitric oxide can promote serotonin release, another good reason to be wary of claims that fish oil is beneficial. Serotonin has been shown to be a driver of insulin resistance, and diabetes progression.
“Recent reports showed that acrolein, a metabolite of chemotherapeutic agents, is a TRPA1 agonist, and we have observed that acrolein increased the release of 5-HT [serotonin]…” (Katsura Nozawa, et al., 2009)
Acrolein, nitric oxide, and serotonin aside, there are numerous other reasons to be concerned about what happens when you consume lots of omega-3 PUFAs.
4-hydroxy-2-hexenal [4-HHE] is another thing that increases throughout the system when fish oil breaks down. 4-HHE promotes oxidative stress, and oxidative stress is a significant promoter of inflammation and disease. Once you understand this, it’s hard not to be skeptical about claims, that fish oil protects against inflammation.
“Trans-4-hydroxy-2-hexenal (HHE) is a major…product of n-3 PUFA oxidation and, like HNE, is an active biochemical mediator resulting from lipid peroxidation. HHE adducts are elevated in disease states…” (Long EK, Picklo MJ Sr., 2010)
“Oxidative stress is involved in the pathophysiology of insulin resistance and its progression towards type 2 diabetes. The peroxidation of n-3 polyunsaturated fatty acids produces 4-hydroxy-2-hexenal (4-HHE), a lipid aldehyde with potent electrophilic properties able to interfere with many pathophysiological processes…4-HHE is produced in type 2 diabetic humans…and blunts insulin action in skeletal muscle. 4-HHE…plays a causal role in the pathophysiology of type 2 diabetes and might constitute a potential therapeutic target to taper oxidative stress-induced insulin resistance.” (Soulage CO, et al., 2018)
Malondialdehyde (MDA) is another well known product of the breakdown of fish oil (and PUFAs in general), and there is a great deal of science which shows a direct connection between rising levels of MDA, and many inflammatory disease states, including diabetes, sepsis, stroke, heart disease, traumatic brain injury, and breast, lung, and other cancers.
“Marine long-chain polyunsaturated fatty acids…are rapidly oxidized, generating highly reactive malondialdehyde (MDA), 4-hydroxy-2-hexenal (HHE) and 4-hydroxy-2-nonenal (HNE)…These oxidation products may interact with DNA and proteins, thus possibly leading to impaired cell functions…higher aldehyde levels were reached in the intestinal lumen than in the initial meal, demonstrating that GI digestion promotes oxidation. Hence, epithelial cells may be exposed to elevated amounts of reactive aldehydes for several hours after a meal containing fish oil.” (Larsson K, et al., 2016)
“Herring developed higher concentrations of MDA and HHE during gastric digestion compared to salmon, which initially contained lower levels of oxidation products. Cooked salmon generated higher MDA concentrations during digestion than raw salmon.” (Larsson K, et al., 2016)
“Lipid peroxidation by reactive oxygen species leads to the formation of highly reactive malondialdehyde (MDA), and extensive MDA is found in diabetes…A significant 2-fold increase in serum MDA also correlated the increased IL-25 and IL-8 mRNA in PBLCs of diabetic patients…These new results suggest that MDA can promote lymphocyte activation via induction of inflammatory pathways and networks.” (Raghavan S, et al., 2012)
“Oxidative stress has been implicated in the pathogenesis of sepsis-induced organ dysfunction…The presence of high serum MDA levels supports the hypothesis that increased oxidative stress, particularly lipid peroxidation, contributes to sepsis pathophysiology.” ( Scott L Weiss & Clifford S Deutschman, 2014)
“MDA levels increased in type 2 diabetes, especially in patients on insulin therapy. Chronic hyperglycemia and other biomarkers, such as urinary albumin, were correlated with MDA levels, suggesting the involvement of lipid peroxidation in the pathogenesis of diabetes complications.” (Kaefer M, et al., 2012)
“Plasma MDA levels in cancer patients were significantly higher than those in controls…Average MDA levels were 6.33 micromol/L in breast cancer patients and 5.87 micromol/L in lung cancer patients…further evidence of the relationship between lipid peroxidation and cancer…” (Gönenç A, et al., 2001)
Crotonaldehyde, like acrolein, is another by-product of the break down of fish oil, which has been connected to the progression of inflammation and disease, including cancer and Alzheimer’s.
Yes, there are other ways (apart from breakdown of PUFAs) to increase exposure to many of these substances (like smoking for instance), but this does not detract from the significance of the enormous increases in consumption of PUFAs, over the last few decades.
“Several studies have documented the involvement of oxidative stress represented by lipid peroxidation in the pathogenesis of Alzheimer’s disease (AD)…Our results suggest that increased oxidative stress and CRA [crotonaldehyde] formation in glial cells is implicated in the disease processes of AD.” (Kawaguchi-Niida M, et al., 2006)
The fish oil breakdown products, isoprostanes and neuroprostanes, have also been shown to play a role in the development of inflammation and oxidative stress, as well as the progression of a variety of disease states, including the neurodegenerative diseases, multiple sclerosis, Alzheimer’s disease, Huntington’s disease, Creutzfeldt-Jakob disease, and Amyotrophic lateral sclerosis (ALS).
I’m not a doctor or nutritionist, and I’m not claiming to know the ins and outs of every single possible biological reaction to fish oil consumption (or PUFAs consumption in general), but these are some arguments that make sense to me, in light of what I have seen and read and experienced.
Have a look for yourself, and if you can find someone who can explain away all of these glaringly obvious contradictions to the ‘fish oil is protective’ hypothesis, let me know. In the meantime, do you really want to be adding more PUFAs into the mix, than is absolutely necessary?
Avoiding consumption of fish oil (and all other PUFAs), makes sense to me as a rational approach to protection from type II diabetes, cancer, and Alzheimer’s. Sufficient ingestion of sugar is protective, in part by preventing the release of stored PUFAs into the blood, by limiting exposure to stress substances, and by promoting production of the anti-inflammatory saturated and omega-9 fats.
Although the saturated fats released into the bloodstream (either from storage in the tissue or from the consumption of fatty food), can also interfere (at least temporarily) with the ability of the cell to oxidize sugar, they are very stable. Because of this, they do not easily break down (like PUFAs) into the toxic chemicals, thereby allowing the cell to return to the proper use of sugar for fuel, when sugar becomes available again.
Oxidative stress, resulting from exposure to the breakdown products of fish oil and other PUFAs, promotes inflammation, and interferes with thyroid energy metabolism. Suppressed thyroid function encourages the release of the stress substances, nitric oxide and serotonin, and has been shown to be involved in the progression of the inflammatory illnesses, including diabetes, cancer, and Alzheimer’s.
“…a group of patients with primary hypothyroidism…found high plasma levels of malondialdehyde (MDA), an OS [oxidative stress] marker that is formed by lipid peroxidation, and NO [nitric oxide]…Elevated MDA levels were also shown in subclinical hypothyroidism…OS seems to be an important mechanism underlying the progress of inflammation. A vicious circle creates a link between these two conditions. Thyroid hormones can have a protective role…on the other side…hypothyroidism can worsen OS.” (Mancini A, et al., 2016)
Sugar promotes thyroid function and protects against the excessive release of nitric oxide and serotonin, and so in this sense alone, it can be understood to be a genuinely anti-inflammatory, anti-stress, disease protective substance.
All of this adds further weight to arguments against fish oil (and PUFAs in general), being something you want to have more of when you are unwell, or at any other time for that matter. But if you are still looking at disease through the eyes of mistaken biological results or interpretations, it’s understandable that you will see things in the exact opposite way.
Restricting sugar, and increasing exposure to the breakdown products of PUFAs of any kind, (interfering with the ability of the cell to oxidize glucose), causes many stress substances to be released (including cortisol, adrenaline and lactate), in greater amounts than would normally be the case, promoting the release of more PUFAs out of storage, and creating a vicious circle type scenario, of gradually worsening metabolic function.
These kinds of stressful circumstances, encourage the progression of diabetes symptoms, including worsening hyperglycemia, insulin resistance, and other blood sugar dysregulation issues, leading to misconceived ideas which make it seem logical to place the blame upon sugar. If you think your health practitioner has looked into these subjects deeply, you might want to think again.
“4-Hydroxynonenal (4-HNE), a relevant lipid peroxidation by-product…may affect several metabolic processes…4-HNE significantly stimulated lactate production by…adipocytes…adipose cells are highly sensitive to oxidative stress, with subsequent…increased lactate production…involved in the development of insulin resistance.” (Soares AF, et al., 2005)
One possible alternative therapeutic approach out there, has involved experimentation with the gradual increase in use of white sugar and honey (in combination with protein, minerals, and other nutrients necessary for a properly functioning metabolism), from sources such as sweet ripe juicy fruits and fruit juice, milk, cheese, and gelatin, whilst at the same time avoiding as much as possible, the consumption of the polyunsaturated fish and seed oils, and too much of the difficult to digest, stress promoting grains, seeds, nut, beans, and under cooked vegetables.
Such a diet has been shown to be able to help protect against stress and inflammation, and prevent the excessive release of PUFAs from storage, increasing exposure to the anti-inflammatory, pro-metabolic fats. Some production of the saturated and omega-9 fats (due to increased sugar consumption and decreased exposure to PUFAs) has also been shown to assist in protecting against the by-products of the breakdown of fish oil and other PUFAs, and with improving the ability of cells to come back to the proper utilization of glucose for fuel, helping the body to slowly rid itself of toxic substances (including stored PUFAs) via safer means, allowing metabolism to function better.
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Image: Allcinema: “Vampire Fish River Monsters”