Alzheimer's DiseaseIntroduction
What Causes AD?
Vitamins B6, B12 and folate
Omega 3
Vitamin D


This is part one of a two part article. Part two can be read here.


Dementia affects one in 14 people in the UK over the age of 65,1 and with average UK life expectancy projected to rise to over 88 by 2062,2 it will be an on-going issue in future society. By far the most common cause of dementia is AD, which accounts for approximately 50–70% of cases.3

With any condition where adequate medicinal treatments are not currently available, patients will look for other options, both to treat and prevent. There has been a long-standing interest from the scientific community as to whether dietary supplementation could be the answer, and this has been widely reported in the media. Given 90% of the British population (aged 15 and over) access news, either in print or online format,4 there is the potential for people who don’t have a scientific background to be easily influenced, especially considering the media’s tendency towards sensationalism.

But do supplements work and if so which ones? This is a common consultation question and one that must be met with evidence-based response to save patient’s time, money and potential harm.


What causes AD?

For much of medicine an understanding of the pathophysiology of a disease leads to management solutions. This is not the case in AD. Currently, there are two main schools of thought; the Amyloid Cascade Hypothesis and the Tau Hypothesis.3,5

The amyloid cascade hypothesis states that AD is caused by the deposition of beta-amyloid protein, predominantly in areas of the brain associated with cognition and memory.3 These depositions aggregate to form extracellular amyloid plaques, which results in; neuronal death, atrophy, inflammation, neurotransmitter inhibition, tau protein dysfunction and subsequently dementia.5

The dysfunction of tau protein leads to its build-up in the cell bodies of neurones forming neurofibrillary tangles.3,5,6 Neurofibrillary tangles are strongly associated with cell death and their quantities are thought to be proportional to the severity of dementia.3

Unlike the amyloid hypothesis, the tau hypothesis proposes that AD is initially and predominantly caused by the development of neurofibrillary tangles, which then begin the disease cascade.3,6,7

Although it is not yet clear which, if either hypothesis is correct, the evidence suggests that both amyloid plaques and neurofibrillary tangles have an important role to play in the development of Alzheimer’s.3,6,78 Therefore, any methods to reduce either would likely have a positive effect.



Headline: “Having a curry could help ward off dementia.” The Daily Telegraph9

Turmeric is a bright yellow spice derived from the rhizome of a plant in the ginger family and is commonly found in Indian cuisine. It contains a polyphenol compound called curcumin, which has attracted considerable interest from the scientific community and media in relation to AD3 because of its four main properties. Firstly, studies in transgenic mice have shown curcumin acts as an anti-amyloid, binding to beta amyloid protein and inhibiting its aggregation.10,11,12 Secondly it also prevents tau protein phosphorylation, a key component in the development of neurofibrillary tangles.6,10 Thirdly, curcumin has an anti-inflammatory effect through its inhibition of pro-inflammatory enzymes such as cyclooxygenase-2 and 5-lipooxygenase.12,13,14 It has been shown that people with AD have measurably higher levels of brain inflammation than those who do not, suggesting that anti-inflammatories and thus curcumin, may have a role to play in prevention.13 Fourthly, it acts as a potent antioxidant, removing free radicals from the brain.3,11 Free radical build up is associated with ageing as the body’s natural antioxidants become less effective and can cause cell death, as well as increasing the susceptibility of neurones to other damage including inflammation.3 Furthermore, oxidative stress from free radical damage has been strongly linked with the early stages of AD.8 This would suggest that using a supplementary antioxidant could be beneficial in both slowing normal cognitive decline in the elderly, and reducing the prevalence of AD.

Is it effective?

One issue with curcumin is that it exerts a very low bioavailability, which means that adequate brain concentrations are difficult to reach.3,12,13 Although curcumin has a low toxicity profile at standard doses, there are concerns that at the high concentrations used in clinical studies it could be dangerous, and therefore the studies are not giving an accurate representation of how well it would actually work.12

On the other hand, with epidemiological studies showing far lower rates of neurodegenerative diseases such as AD in areas where high levels of turmeric are consumed, (eg. India),141516 there may be an argument that long-term use of turmeric is beneficial. However, it is important to mention that this may just be a coincidental link rather than causal.

In summary, it is very unlikely that having a curry once a week will reduce the chance of developing AD and in fact with the high levels of saturated fat and cholesterol in many UK curries, it may actually do more harm than good. In terms of turmeric/curcumin supplements, due to their low bioavailability they are probably ineffectual. However, it is clear that curcumin does possess properties that may in the future be used in either the prevention or treatment for AD, although this may need to be in combination with other substances.12


Vitamins B6, B12 and folate

Headline:“Vitamin B could stave off Alzheimers.” The Daily Telegraph17

Vitamins B6, B12 and folate play many vital roles in the body, including aiding in: DNA synthesis, metabolism, erythropoiesis and maintaining normal brain function18 With regards to AD, it is the link between them and the amino acid homocysteine that has attracted interest.

Homocysteine acts as an intermediate in protein metabolism, where it is then broken down in reactions that require vitamins B6, B12 and folate. Deficiencies in these vitamins can result in a build-up in homocysteine levels, which has been linked with both vascular and cognitive diseases including AD. Although no definitive causal relationship between homocysteine and AD has been proven, researchers believe that high serum homocysteine can lead to an increase in brain atrophy,19,20 and also has potential neurotoxic effects.21 Because of this, it has been hypothesised that supplementation with these vitamin B subtypes would reduce these processes, therefore potentially slowing the progression to AD.20,22,23

Is it effective?

The study that sparked the majority of media reports concluded that high dose vitamin B supplements significantly reduced grey matter atrophy in areas of the brain that are particularly vulnerable to damage in AD.22 However, firstly it demonstrated that grey matter atrophy rates were only reduced in patients that had higher than average serum homocysteine levels. High serum homocysteine is associated with deficiencies in vitamin B,23,24 so it is therefore possible that all the researchers did was replace the vitamin B that these participants were deficient in. As vitamins and minerals are vital for normal function, it would be expected that replacing this deficiency resulted in positive brain changes. Secondly, it was unclear from the study whether or not the decrease in grey matter atrophy was associated with any cognitive improvement for the patients. This corroborates with other studies, which have also found little to no increase in cognition from taking vitamin B supplements.25,26,27

In summary, further research is required to establish whether there is a causal link between elevated homocysteine and AD. Deficiencies in vitamin B can affect normal brain function23 and should therefore be treated appropriately. However, the evidence does not suggest any benefit in additional supplementation if their dietary intake is sufficient.25,26,27


Omega 3

Headline: “Fish oil could help prevent Alzheimer’s and also give you a bigger brain,” The Daily Mail28

Omega 3 PolyUnsaturated Fatty Acids (PUFAs) are essential fatty acids and can therefore not be synthesised naturally in the body.29 They are found in foods such as; fish oil, walnuts, flaxseed and can also be bought in supplement form.

It is thought that omega 3 may play a protective role within the brain, maintaining membrane integrity, neurogenesis and mediating potentially damaging processes such as inflammation or oxidative stress.29 Therefore, it is plausible to hypothesise that consuming more omega 3 could slow the progression of a progressive brain disease such as AD, or even prevent it entirely.

Is it effective?

The evidence for the effectiveness of omega 3 is contradictory. Some observational studies show benefits, but this is not consistent with data from randomised controlled trials. The Cochrane review assessing the effectiveness of omega 3 PUFA supplementation in preventing dementia or slowing mental decline in cognitively healthy people, found no benefits.29

In summary, there is currently no conclusive evidence to state that omega 3 supplements have any long term effect on cognition.29,30,31,32


Vitamin D

Headline: “Alzheimer’s risk doubles with lack of vitamin D - and upping intake could prevent disease.” The Daily Mirror33

Vitamin D is an essential micronutrient, primarily responsible for the maintenance of serum calcium and phosphate levels, vital for normal bone mineralisation and remodelling. It also plays a part in regulating cell growth, immune function and reducing inflammation.34 The majority of our vitamin D comes from sunlight, with a small proportion coming from food, in particular oily fish. It is also available in supplement form.34,35

A body of research is emerging that suggests the potential roles of vitamin D extend far beyond what has been previously discussed. For example, epidemiological studies seem to show that vitamin D could be a protective agent against cardiovascular disease, diabetes, cancer and more recently cognitive decline.36 With respect to cognitive decline, there are a number of reported biological mechanisms to explain the association.

Firstly, it is important to recognise that vitamin D plays an active role within the brain including in the hippocampus and dentate gyrus, areas involved in memory. Although the full extent of this is not yet understood, it is thought that vitamin D is involved in the regulation of both neural cells and pro-inflammatory cytokines. Secondly vitamin D deficiency is believed to result in increased brain inflammation and dysfunction of neural cells, both of which would contribute to cognitive decline. Thirdly, vitamin D is predicted to have an anti-oxidative effect on the brain,36,37 another possible neuroprotective mechanism. Fourthly, looking at the pathogenesis of AD specifically, new research shows that in vitro vitamin D can both interfere with the production and promote the clearance of amyloid plaques.38

Is it effective?

Much like the role of vitamin B in the prevention of AD, current evidence for vitamin D’s effectiveness is based on people with deficiencies.36,34,39,40,41,42 In fact, research has found little to no benefit in vitamin D supplementation when serum levels are adequate.35

However, unlike vitamin B6, 9 and 12 deficiencies, which are relatively uncommon in the western world for people under the age of 65 years,43,44,45 vitamin D deficiency is far more prevalent.3,42

A national survey into the white British population found that 60.9% of participant’s had concentrations of 25OHD below 75nmol/L during the summer and autumn, with that number rising to 87.1% during the winter and spring.42 However, there is debate as to what 25OHD concentration constitutes a deficiency. The Endocrine Society uses the value of 75nmol/L, but the Institute of Medicine suggests a lower concentration of 50nmol/L. Without knowing exact values, it is impossible to predict the true scale of the problem, or devise effective management strategies.

Whilst there is debate about the cut off, the statistics show that there is significant vitamin D deficiency within the population (ie. less than 25nmol/L).46 In terms of AD prevention and treatment the evidence is still at a very early stage and mainly epidemiological, so currently there are too many variables to suggest a causal relationship.47,48



This report is not an exhaustive compilation of the current supplements claiming to promote cognitive enhancement as each supplement has its moment in the media spotlight before a new one appears. The supplements examined show that, despite the significant media speculation, there currently is not an evidence based product on the market that has demonstrated prevention, or slowing the progression of AD. In summary, this report should give clinicians more confidence to provide evidence-based responses to patient’s questions about the effectiveness of many products in the market that claim to ‘ward off’ AD.


Dominic Dewson, 4th Year Medical Student at Plymouth University Peninsula School of Medicine and Dentistry
Allison O'Kelly, Queen’s Nurse. Clinical Lead, East Cornwall Memory Services, Cornwall Foundation Trust
Dr Giles Richards, Consultant Psychiatrist, Cornwall Foundation Trust

Conflict of interest: none declared

Part two will published in the March edition and will examine further supplements and their evidence base.


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