We are all aware of the benefits of omega-3 for brain health, but its benefits in Alzheimer’s are debatable.
Omega-3 fatty acids are polyunsaturated essential fatty acids that we do not produce in our body and derive from the diet.
Fatty fish like salmon are rich sources of these fatty acids, but there are plant and algal sources as well.
The important omega-3 fatty acids are alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).
They are metabolised in the body to form eicosanoids, and these play an important role in inflammation and platelet aggregation.
Arachidonic acid is one of the principal agents involved in inflammation. EPA and DHA compete with arachidonic acid for production of eicosanoids and result in reduced inflammatory activity. To know more about omega-3 fatty acids, please check this excellent resource.
Omega-3 fatty acids are essential for brain health since our brain is nearly 60 % fat. Omega-3 fatty acids help in early stages of Alzheimer’s and in Mild Cognitive Impairment. Experimental studies reveal many benefits of omega-3s for Alzheimer’s but these have not been translated in human studies.
Before we get to that, let’s examine the benefits of omega-3 for Alzheimer’s.
6 Proven Benefits Of Omega-3 For Alzheimer’s
The need to rectify the deficiency of essential fatty acids and their anti-inflammatory effect contribute to the therapeutic benefits of these fatty acids in Alzheimer’s.
1. They reduce inflammation in the brain
Metabolism of omega-3 fatty acids in the body leads to the production of many intermediates that can interfere with the inflammatory process and reduce inflammation.
Alzheimer’s disease is characterised by inflammation in the brain. Thomas et al. conducted a review study and hypothesized that early management of inflammation could help reduce or delay the onset of symptoms of dementia.
Aging brain can have lower levels of essential fatty acids, and in Alzheimer’s, the brain is deficient in DHA. Hence DHA supplementation can reduce inflammation. And a few studies reviewed by them, actually demonstrated that early supplementation with omega-3 might prevent Alzheimer’s.
A recent study published in Advances in Nutrition, 2016 states that both EPA and DHA can resolve inflammation in the brain; but EPA benefits in mood disorders and DHA maintains brain structure.
Oxylipins are anti-inflammatory mediators derived from omega-3 that can help in curbing inflammation in Alzheimer’s.
In the OmegAD study, 2.3g of omega-3 fatty acid supplementation daily for 6 months resulted in no significant benefit on inflammatory parameters in the disease. However further research demonstrated that they influenced genes involved in inflammation.
Quick Gist: Omega-3 fatty acids interfere in the inflammatory cascade and lead to the production of anti-inflammatory agents. This can help counteract neuroinflammation in Alzheimer’s.
2. They may help protect cognition in early stages
Experimental animal studies demonstrate that omega-3 supplementation improves cognition and reduces brain cell loss in Alzheimer’s.
These fatty acids protect cognition by clearing amyloid beta plaques. However, as per the study published in FASEB Journal, 2015 this effect is observed in patients with mild cognitive impairment and not in Alzheimer’s disease patients.
Similarly, a group of researchers from Taiwan treated patients with Alzheimer’s disease and mild cognitive impairment with 1.8g of omega-3 per day. Interestingly patients with mild cognitive impairment showed a reduced cognitive decline, but this was not observed in Alzheimer’s disease patients.
Researchers from Oregon Health & Science University conducted a study in 2010 where they treated Alzheimer’s disease patients with 2g algal DHA daily for 18 months. But, DHA supplementation was found to be ineffective in reducing cognitive decline in the patients.
Further in 2014, the same group of researchers conducted another study where they treated patients with Alzheimer’s dementia with omega-3 or omega-3 + ALA or placebo.
It was observed that omega-3 supplementation reduced only cognitive decline while omega-3 and ALA combination reduced cognitive and functional decline. The Omega-3 supplement used was a fish oil concentrate containing 675mg DHA and 900 mg EPA.
Results of the OmegAD study (2015) also reported that higher the plasma omega-3 levels, lower the rate of cognitive decline.
Quick Gist: Omega-3 fatty acids have cognition enhancing effects, and these are pronounced during early stages of Alzheimer’s.
3. Dietary and marine derived omega-3 fatty acids reduce risk of Alzheimer’s
Researchers from Rush Institute for Healthy Aging studied the dietary habits of 815 individuals and followed up for 3.9 years.
131 individuals developed Alzheimer’s disease. Individuals who consumed fish once per week or more were 60% less likely to develop Alzheimer’s than those who rarely ate or did not consume fish.
Total intake of omega-3 fatty acids was linked with Alzheimer’s disease, but no specific links between EPA and DHA intake were found.
Zhang et al. recently published their findings in The American Journal Of Clinical Nutrition, 2016. As per their evaluation, consumption of fish products was associated with reduced cognitive impairment and DHA from marine products reduced the risk of Alzheimer’s and dementia.
A recent study published in Journal of Alzheimer’s Disease, 2016 reported that omega-3 fatty acid levels in the body could affect the effectiveness of vitamin B therapy for restoring cognition.
Low levels of omega-3 in the body make vitamin B therapy ineffective; normal levels of omega-3 help vitamin B supplementation ameliorate cognitive decline.
The Alzheimer’s Association conducted a neuroimaging study where they assessed the effect of fish oil supplementation in Alzheimer’s disease via a brain scan.
Fish oil supplementation was found to preserve brain volume in Alzheimer’s patients but did not affect cognition. Also, this effect was more pronounced in those who did not carry ApoE ε4 genes.
ApoE is a gene involved cholesterol transport and has multiple alleles or forms. Those carrying the ε4 form are at a higher risk of developing Alzheimer’s.
Quick Gist: Certain epidemiological studies demonstrate that regular fatty fish intake can reduce the risk of dementia. Also, the omega-3 fatty acid status can affect the therapeutic actions of other vitamins in neurodegenerative disorders.
4. Experimental studies reveal that omega-3 can help clear amyloid beta plaques
In normal individuals, amyloid beta clearance is supported by immune cells in the brain. But in those with mild cognitive impairment, this ability is impaired and could occur as a result of the genetic effect.
Various receptors are involved in cholesterol and lipid transport in the brain. Activation of these receptors can help clear amyloid beta plaques and reduce inflammation. Bexarotene is one such agent used to activate these receptors.
Essential fatty acids, when used in combination with bexarotene, help in clearance of amyloid beta plaques and reduce the formation of inflammation causing agents in the body. This can reduce pathological symptoms of the disease and prevent cognitive decline.
Research suggests that omega-3 supplementation can lead to the formation of agents that assist in amyloid beta clearance but this effect is only pronounced in patients with mild cognitive impairment and not those with Alzheimer’s disease.
These fatty acids regulate immune cells and promote their activity to clear amyloid beta plaques.
Quick Gist: Omega-3 fatty acids may regulate the immune system’s activity and stimulate immune cells to clear amyloid beta plaques.
5. It improves overall health in Alzheimer’s
204 patients with mild to moderate Alzheimer’s disease were treated with 1.7g DHA and 0.6g EPA or placebo for 6 months. After 6 months, all patients received omega-3 fatty acids for another 6 months.
Body weight and BMI increased in patients treated with omega-3. Body weight did not change in the placebo group during the first 6 months but once omega-3 supplementation was initiated their weight increased.
Appetite also improved in the essential fatty acid group. The absence of APOE ε4 gene and high plasma levels of DHA were found to be linked with weight gain in the patients.
Quick Gist: Omega-3 fatty acid supplementation may help prevent weight loss and restore appetite in Alzheimer’s.
6. Omega-3 are natural neuroprotective agents
Omega-3 fatty acids are neuroprotective and can protect from a neuronal loss in neurodegenerative diseases.
Their anti-inflammatory activity helps prevent the immune cells in the brain from triggering and worsening inflammation in Alzheimer’s. They exert an indirect antioxidant action by regulating proteins involved in the occurrence of oxidative stress in brain tissue.
These properties reduce the accumulation of amyloid beta and result in a neurotrophic effect (support growth of neurons).
Neuroprotectin 1 is one of the derivatives of these essential fatty acids that benefit in Alzheimer’s disease in the following ways :
• Stimulates the production of enzyme secretase to clear amyloid beta plaques
• Exerts an anti-inflammatory effect
• Protects neurons from cell death in Alzheimer’s
Quick Gist: Omega-3 may help prevent neuronal loss in Alzheimer’s.
Some studies in humans show that omega-3 supplementation may not benefit in Alzheimer’s
Despite these positive effects, many studies have reported that omega-3 fatty acid supplementation does not result in improvement of clinical symptoms in Alzheimer’s. Here is a quick tabulated form of some these studies:
|Author & Date||Dosage of omega 3 fatty acids||Results|
|Kotani et al., 2006||240 mg of arachidonic acid and DHA for 90 days||No improvement in Alzheimer’s disease patients, improvement in attention and cognition only in patients with mild cognitive impairment|
|OmegAD study, Freund-Levi et al., 2006||1.7g DHA or 0.6g EPA for 6-12 months||No improvements in patients with mild to moderate Alzheimer’s; positive effects observed only in patients with very mild Alzheimer’s|
|Freund-Levi et al., 2008||1.7g DHA or 0.6g EPA for 6-12 months||No significant reduction in psychiatric symptoms; slight reduction in depressive and agitation symptoms in individuals who did not carry ApoE ε4 gene|
|OmegAD study, Freund-Levi et al., 2014||1.7g DHA or 0.6g EPA for 6 months||No obvious effect on oxidative stress and inflammation in Alzheimer’s|
|Phillips et al., 2015||600 mg EPA and 625 mg DHA per day for 4 months||No significant benefits observed in those with cognitive impairment or dementia|
Why do omega-3 fatty acids not benefit in Alzheimer’s?
Though omega-3s have many benefits for brain health, clinical trials have found that supplementation with omega-3s does not help in late Alzheimer’s. Researchers have identified various causes for discrepancy regarding the effectiveness of omega-3 therapy in Alzheimer’s.
1. Individual omega-3 fatty acids may be more effective than combination
A study published in Frontiers In Aging Neuroscience, 2015 suggests that researchers must take into account individual role of EPA, DHA and DPA and their independent actions towards protecting the aging brain from neurodegenerative disorders.
The author points out that Alzheimer’s patients have lowered DHA and DHA supplementation may help lower inflammation in addition to rectifying this deficiency. But coming to clinical trials, patients treated with EPA (1g/day) showed no significant clinical benefits.
Similarly, when treated with DHA (2g/day), no reduction in cognitive decline was observed in patients with mild to moderate Alzheimer’s.
However, the OmegAD study (2015) utilised a DHA rich omega-3 supplementation. Their results showed that increase in plasma levels of omega-3 helped lower the rate of cognitive decline in the patients.
Though EPA and DHA may have separate roles when protecting brain health, there is no clear consensus as to whether supplementation with pure individual fatty acids may benefit in Alzheimer’s.
Quick Gist: Researchers feel that individual omega-3 fatty acids may play different roles in amyloid beta plaque formation. Hence essential fatty acid supplements enriched with one particular fatty acid may be beneficial than the combination. But this is not proven via human studies.
2. Fish oil may be more effective than purified omega-3 supplements
It is highly likely that consumption of fatty fish on a regular basis may increase the effectiveness or absorption of omega-3 fatty acids.
A study published in The American Journal of Clinical Nutrition, 2009 that fish intake and omega-3 fatty acid consumption may not be associated with long term risk of developing dementia. Their analysis revealed that those who had high fish intake have a similar risk of dementia as those who ate fatty fish.
Various studies have proved that omega-3 fatty acids levels are reduced in patients with Alzheimer’s disease and cognitive impairment. Hence supplementation seems to be a solution.
Phillips et al. have put forward an interesting point. They state that lower omega-3 fatty acid level is linked with increased cognitive decline. But it is highly likely, that this lowering of essential fatty acids could have occurred due to changes in diet after the onset of cognitive decline.
These findings give rise to the chicken and egg story, but it is one aspect that should be investigated further.
Coming back to the point, that omega-3 in fish oil or fatty fish may be more effective as they contain other nutrients that support their efficacy. A study published in PLoS One, 2011 demonstrated that DHA in combination with low-fat diet helped in clearing amyloid beta plaques.
The study concluded that researchers need to take into account the presence of other nutrients or mixed lipids and their effect on amyloid beta plaques.
Souvenaid is a medical food that contains omega-3 fatty acids in addition to other nutrients. Results of clinical trials suggest that Souvenaid improves memory in patients with mild Alzheimer’s and who have not been treated with conventional medication.
These findings are a contrast to the previous point where researchers suggest that one should consider roles of individual fatty acids.
Quick Gist: Fish oil is found to be more beneficial, and this may be due to the presence of other nutrients and mixed lipids. This is in contrast to the previous point. However, this reveals that only focusing on fatty fish inclusion without considering other dietary factors may not be beneficial in reducing dementia risk.
3. Omega-3 fatty acids may not cross blood brain barrier
Research studies have pointed out various benefits of DHA in preclinical studies:
• Reduced amyloid beta plaque and tau accumulation
• Reduced inflammation in the brain
• Improved cognition
But these are not translated into human clinical trials. Pan et al. suggest that perhaps the blood brain barrier impairs the beneficial effects of DHA in Alzheimer’s.
In this disorder, the brain has low levels of DHA, and since the brain cannot synthesize DHA, it obtains DHA from the plasma. However, it is hypothesized that in Alzheimer’s, there is the reduced transport of DHA across the blood brain barrier and hence the resultant cognitive decline.
Results from OmegAD study throw some light on this point. Patients were treated with 2.3g omega-3 fatty acids rich in DHA for 6 months.
An increase in EPA and DHA levels was observed in the cerebrospinal fluid (the fluid present in the spinal cord and brain that provides nutrition and immunity). Higher the levels of DHA, more significant was the change in inflammatory markers of the disease.
The increase in omega-3 fatty acids levels was suggestive of the fact that DHA crosses blood brain barrier, but no clinical improvement was observed.
Since this a single study exploring this point, more research is required on this aspect.
Quick Gist: Researchers hypothesize that the blood brain barrier may hinder transport and efficacy of omega-3 in Alzheimer’s. Further research is required to this point.
4. Presence of certain genes may make omega-3 therapy ineffective
Previously I have mentioned about the ApoE gene. This gene is responsible for transport of cholesterol and lipids to the brain. It has different forms or alleles; one of them is ε4 allele.
This ε4 allele is a major risk factor for late onset Alzheimer’s. Since this gene is involved in fat metabolism, it may affect the efficacy of omega-3 fatty acid therapy.
Pascale et al. have listed various reasons for this in their research paper ‘Dietary omega 3 polyunsaturated fatty acids and Alzheimer’s disease: interaction with apolipoprotein E genotype’.
Quick Gist: The presence of ApoE ε4 gene increases the risk of developing Alzheimer’s. Various studies have found that omega-3 fatty acids may benefit only non carriers of ApoE ε4 and during early stages of Alzheimer’s dementia.
5. Omega-3 supplementation may be effective only at early stages
If you have closely paid attention to the clinical trials I have listed in the earlier sections, many of them have found a slight improvement in memory and reduction in cognitive decline in patients with mild cognitive impairment and NOT in Alzheimer’s patients.
A 12-month supplementation with fish oil enriched in DHA is found to improve memory in patients with mild cognitive impairment significantly.
Omega-3 fatty acid supplementation may be beneficial in halting the disease at very early stages. With disease progression, there could be a change in metabolism, or perhaps interference from conventional treatment can interfere with the omega-3 therapy.
Quick Gist: Omega-3 fatty acid supplementation helps in reducing cognitive decline specifically in patients with mild cognitive impairment. These benefits are not observed in patients with mild to moderate Alzheimer’s.
Dosage of Omega-3 for Mild Cognitive Impairment or Early Alzheimer’s
There is no specific dose of omega-3 prescribed for Alzheimer’s. Fish oil is one of the best sources; a good vegetarian source is algal derived omega-3.
Studies have utilised a dose of 1.8-2g of omega-3 [1.3-1.7mg DHA and 0.45-0.6mg EPA] per day in case of mild cognitive impairment or early stages of Alzheimer’s disease.
Belching is a very common side effect of fish oil consumption. To avoid this, please take the capsules right after meals and avoid consuming any excess amount of liquid after it.
Please consult a health practitioner before taking omega-3 supplements for Alzheimer’s.
Allergies are possible with omega 3 consumption. If you suffer from seafood allergies, avoid fish oil.
Gastric discomfort and acid reflux like symptoms are possible with omega-3 supplements. Start with small doses and scale up gradually. Also consume it immediately after meals to avoid belching.
High doses of omega-3 may increase bleeding risk. Avoid if suffering from the bleeding disorder and if taking blood thinners.
Omega-3 fatty acids may have drug interactions with blood thinners, NSAIDs, steroids, cyclosporine, diabetes medications and cholesterol lowering drugs.
Ensure that omega 3 capsules are a good brand and free from heavy metal contamination. Consult your health practitioner before taking omega-3 capsules.
Omega-3 capsules are proven to be beneficial for brain health and efficacious in preventing neurodegenerative diseases as per pre-clinical studies. Dietary essential fatty acids along with other nutrients can aid in reducing dementia risk.
Human studies have not demonstrated clear benefits of omega-3 supplementation in mild to moderate Alzheimer’s. However at early stages, and during mild cognitive impairment, they can improve memory and reduce cognitive decline.
Researchers are identifying various reasons as to why essential fatty acid supplementation has not shown clinical benefits. Some them include nutrient-gene interaction, the progression of the disease or perhaps need to include other nutrients to increase omega-3 efficacy.
Another intriguing point that requires research is that do conventional medicines for Alzheimer’s affect the efficacy of omega-3 or do their long term therapy, or even disease progression bring about changes in the body that render Omega -3 supplementation ineffective.
Till we get an answer on that, it is safe to conclude that omega-3 can benefit in mild cognitive impairment and early stages of Alzheimer’s. They can help prevent and reduce the risk of developing Alzheimer’s.
Dietary inclusion of essential fatty acids is still recommended for mild to moderate Alzheimer’s.