In the UK progress in putting these breakthroughs into action is slow. The two leading charities, the Alzheimer’s Society and Alzheimer’s Research UK (ARUK) fail to mention the importance of homocysteine lowering B vitamins and omega-3 at all and have confirmed that they are not funding any research on their use in prevention or planning to do so. ARUK’s chief medical officer Professor Jon Schott and the Alzheimer’s Society’s associate director of research, Richard Oakley, declined to comment.
ARUK’s Brain Health Check-In, a short 13 question check list, with only one very basic question on diet, says nothing at all about B vitamins or whether or not a person supplements omega-3 fish oils despite ARUK having part-funded the Oxford University research. According to Professor Smith, who was the first Chair of their Scientific Advisory Board “ARUK part-funded our trial on B vitamins, and are aware of the results. I don’t understand why they make no mention of such an effective preventive intervention, that is taking a 10p a day B vitamin supplement if your homocysteine is high. Now we know that those who also supplement with omega-3 fish oil, or eat fish regularly, reduce their risk. These are the easiest two prevention actions anyone can take, with a significant impact on reducing the risk for dementia. Everyone needs to know this.”
“We’ve been applying to UK and EU agencies for the past 8 years to fund the obvious next trial – testing the effects of B vitamins and omega-3 combined to see if they slow, or prevent, conversion from cognitive impairment to dementia, but to no avail.” Says Professor Smith.
Neither the Alzheimer’s Society, nor ARUK are funding any vitamin or omega-3 research and spend virtually none of their annual research pot, which exceeded £37 million last year, on diet or lifestyle prevention which offer the most potential, despite these representing up to half of the risk for Alzheimer’s. Neither would confirm the percentage of their research funds that were being spent on prevention research.
UK Government have pledged to deliver ‘Dementia Moonshot’, doubling dementia research funding to £160 million to ‘fast-track the development of new treatments’, meanwhile ignoring the biggest breakthroughs in diet and lifestyle prevention. Most support is feeding failed drug research. With an estimated $50 billion [12] spent so far on amyloid drugs and research, all of which have failed to produce any clinical benefit, isn’t it time governments and Alzheimer’s charities took prevention seriously?
In contrast, the Food for the Brain Foundation are doing just that. “At Foodforthebrain.org we are testing almost 4,000 people every month on our free online Cognitive Function Test, and assessing all risk factors on a 140 question questionnaire, including the need for B vitamins and omega-3. We hope, soon, to introduce a pinprick blood test for both omega-3 and homocysteine. We don’t know why the most evidence-based, easy to action and inexpensive prevention steps are being ignored” says Holford. “Why world class scientists such as Professor David Smith’s team at Oxford University have been unable to get funding for the most essential research is shameful. Right now we know enough to cut the average person’s risk of developing Alzheimer’s by up to two thirds and the number of people developing dementia by a third if only there was the political will to do so.”
One of the reasons for complacency in the UK is the Lancet’s commissioned report on Alzheimer’s prevention chaired by Gillian Livingston, Professor of Psychiatry for Older People, at the University College London (UCL). The report, first published in 2017, didn’t include B vitamins. Despite being sent all the evidence by Smith. The 2020 revised report still excluded this vital research, as did a follow up report specifically on supplements in 2022. “There are no trials that show that lowering homocysteine has any benefit” she told us yet she had been sent the unequivocal evidence that the B vitamins reduced brain shrinkage by up to 73%, compared to the 2% reduction of anti-amyloid drugs and the combination of omega-3 and B vitamins has lowered the Clinical Dementia Rating (CDR) in placebo controlled trials by three times that reported by the recent anti-amyloid drug, Lecanemab. (see charts below).
When asked about the recent finding of a synergistic effect of B vitamins and omega-3 she said “It sounds a good hypothesis. I hope they can get the funding for it, but raised homocysteine is not common in the wider population and drug companies can’t be expected to fund nutrition trials, so money would have to come from some government agency.”
There is one prevention study, called AppleTree, underway at University College London. It focuses on reducing risk for Alzheimer’s by eating a Mediterranean style diet and lifestyle advice, including encouraging smokers to quit, which is a known risk factor for cognitive decline. One recent study shows that being a smoker increases risk for dementia by 1.5 times and quitting for at least 3 years reduces much of that risk. [13] One in twelve people over 65 smoke.
In contrast, almost half of all people over 65 have raised homocysteine [14] which increases risk for cognitive impairment by up to ten times, according to Chinese research published last year[15]. Lowering homocysteine with B vitamins, and sufficient omega-3, would virtually eliminate that risk. This suggests that targeting B vitamins and omega-3 would be about twenty times more impactful in preventing dementia than quitting smoking. Yet the need for supplemental intake of these nutrients is not part of the Apple Tree protocol.
If you’d like to test your cognitive function and find out how to reduce your risk, register here and join our citizen science campaign.
[3] van Soest, A.P.M., van de Rest, O., Witkamp, R.F. et al. DHA status influences effects of B-vitamin supplementation on cognitive ageing: a post-hoc analysis of the B-proof trial. Eur J Nutr (2022). https://doi.org/10.1007/s00394-022-02924-w
[4] Jernerén F, Cederholm T, Refsum H, Smith AD, Turner C, Palmblad J, Eriksdotter M, Hjorth E, Faxen-Irving G, Wahlund LO, Schultzberg M, Basun H, Freund-Levi Y. Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer’s Disease: The OmegAD Study. J Alzheimers Dis. 2019;69(1):189-197. doi: 10.3233/JAD-181148. PMID: 30958356.
[5] Walsh S, Merrick R, Richard E, Nurock S, Brayne C. Lecanemab for Alzheimer’s disease. BMJ. 2022 Dec 19;379:o3010. doi: 10.1136/bmj.o3010. PMID: 36535691.
[6] Li M, Li W, Gao Y, Chen Y, Bai D, Weng J, Du Y, Ma F, Wang X, Liu H, Huang G. Effect of folic acid combined with docosahexaenoic acid intervention on mild cognitive impairment in elderly: a randomized double-blind, placebo-controlled trial. Eur J Nutr. 2021 Jun;60(4):1795-1808. doi: 10.1007/s00394-020-02373-3. Epub 2020 Aug 28. PMID: 32856190.
[7] Yu JT, Xu W, Tan CC, Andrieu S, Suckling J, Evangelou E, Pan A, Zhang C, Jia J, Feng L, Kua EH, Wang YJ, Wang HF, Tan MS, Li JQ, Hou XH, Wan Y, Tan L, Mok V, Tan L, Dong Q, Touchon J, Gauthier S, Aisen PS, Vellas B. Evidence-based prevention of Alzheimer’s disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials. J Neurol Neurosurg Psychiatry. 2020 Nov;91(11):1201-1209. doi: 10.1136/jnnp-2019-321913. Epub 2020 Jul 20. PMID: 32690803; PMCID: PMC7569385.
[8] Huang Y, Deng Y, Zhang P, Lin J, Guo D, Yang L, Liu D, Xu B, Huang C, Zhang H. Associations of fish oil supplementation with incident dementia: Evidence from the UK Biobank cohort study. Front Neurosci. 2022 Sep 7;16:910977. doi: 10.3389/fnins.2022.910977. PMID: 36161159; PMCID: PMC9489907.
[9] Jeong SM, Park J, Han K, Yoo J, Yoo JE, Lee CM, Jung W, Lee J, Kim SY, Shin DW. Association of Changes in Smoking Intensity With Risk of Dementia in Korea. JAMA Netw Open. 2023 Jan 3;6(1):e2251506. doi: 10.1001/jamanetworkopen.2022.51506. PMID: 36656579; PMCID: PMC9857334.
[10] Beydoun MA, Beydoun HA, Gamaldo AA, Teel A, Zonderman AB, Wang Y. Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis. BMC Public Health. 2014 Jun 24;14:643. doi: 10.1186/1471-2458-14-643. PMID: 24962204; PMCID: PMC4099157.
[11] Witte AV, Kerti L, Hermannstädter HM, Fiebach JB, Schreiber SJ, Schuchardt JP, Hahn A, Flöel A. Long-chain omega-3 fatty acids improve brain function and structure in older adults. Cereb Cortex. 2014 Nov;24(11):3059-68. doi: 10.1093/cercor/bht163. Epub 2013 Jun 24. PMID: 23796946.
[12] Cummings JL, Goldman DP, Simmons-Stern NR, Ponton E. The costs of developing treatments for Alzheimer’s disease: A retrospective exploration. Alzheimers Dement. 2022 Mar;18(3):469-477. doi: 10.1002/alz.12450. Epub 2021 Sep 28. PMID: 34581499; PMCID: PMC8940715.
[13] Lu Y, Sugawara Y, Zhang S, Tomata Y, Tsuji I. Smoking cessation and incident dementia in elderly Japanese: the Ohsaki Cohort 2006 Study. Eur J Epidemiol. 2020 Sep;35(9):851-860. doi: 10.1007/s10654-020-00612-9. Epub 2020 Feb 15. PMID: 32060675; PMCID: PMC7525275.
[14] Pfeiffer CM, Osterloh JD, Kennedy-Stephenson J, Picciano MF, Yetley EA, Rader JI, Johnson CL. Trends in circulating concentrations of total homocysteine among US adolescents and adults: findings from the 1991-1994 and 1999-2004 National Health and Nutrition Examination Surveys. Clin Chem. 2008 May;54(5):801-13. doi: 10.1373/clinchem.2007.100214. Epub 2008 Mar 28. PMID: 18375482.
[15] Teng Z, Feng J, Liu R, Ji Y, Xu J, Jiang X, Chen H, Dong Y, Meng N, Xiao Y, Xie X and Lv P (2022) Cerebral small vessel disease mediates the association between homocysteine and cognitive function. Front. Aging Neurosci. 14:868777. doi: 10.3389/fnagi.2022.868777
New research shows that the combination of B vitamins and omega-3 are a dynamic duo against dementia, stopping the brain shrinkage that is the hallmark of Alzheimer’s.
The discovery, hailed as the “a major step towards Alzheimer’s prevention” was first made at the University of Oxford, but has now been confirmed by research groups in Holland, Sweden and China.
Headed by Professor David Smith, former Chair of Pharmacology and Deputy Head of the Division of Medical Sciences at Oxford University and director of the Oxford Project to Investigate Memory and Ageing (OPTIMA), the research has found that giving older people with the first signs of cognitive impairment supplemental B vitamins (B6, B12 and folic acid) at higher levels than can be achieved through diet to those with sufficient omega-3 fats produced 73% less brain shrinkage in a year, compared to placebo. This reduction brought brain shrinkage down to the level found in those elderly with no cognitive decline. The trial was part-funded by Alzheimer’s Research UK (ARUK). “The effect is greater than that of any drug treatment to date – with no adverse effects.” says Professor Smith. In contrast the recent trials of anti-amyloid drugs have reduced brain shrinkage by 2%.
“Brain shrinkage is the hallmark of Alzheimer’s so this was a vital discovery for its prevention” says Patrick Holford, director of the Alzheimer’s Prevention Project at foodforthebrain.org, the UK’s leading dementia prevention charity “However we needed confirmation from other research groups. Now we have it.”.
Three other research groups have confirmed the combined effect of omega-3 and B vitamins is greater than either nutrient on its own.
“You literally cannot build brain cells without both omega-3 fats and sufficient B vitamins” says Holford. “If you give a builder a hammer or a bag of nails you don’t get a house. But if you give them both they can build a house. The B vitamins drive a process called methylation which assembles the critical brain-building fats that make up the membrane of neurons, through which all brain communication happens. Both are vital for building brain cells. Neither can work without the other.”
Watch this one minute film, on how to build new brain cells at any age.
Realising that the combination of B vitamins and omega-3 fats is key, researchers in Holland, who had previously run a major trial called B-proof that had tested the effects of B vitamins on memory but had only found very modest benefits decided to take reanalyse the results of their B vitamin trial according to the participants blood levels of omega-3 at the start of the trial. Sure enough, they found no benefit at all from the B vitamins in those with low omega-3 status, but a massive improvement in cognition in those in the top third of omega-3 levels.[i]
Could this need for both explain why some trials testing omega-3 were also not successful?
The Oxford University researchers, led by Dr Frederik Jerneren, were given access to the blood samples from another trial in Sweden called OmegAD. This trial had given older people a hefty dose of 2.3grams (two large capsules) of omega-3 fish oils. The trial had apparently failed, showing no significant cognitive benefit. Could faulty methylation, a result of lack of B vitamins, be the reason for the omega-3 fish oils not working?
The Oxford researchers therefore measured homocysteine, a consequence of a lack of B vitamins, in the samples from the OmegAD trial. Dr Jerneren split the participants into thirds – from the lowest to highest level of homocysteine. Those given omega-3 who had the lowest homocysteine, in other words sufficient in B vitamins, had a highly significant improvement in their clinical dementia rating while those with high homocysteine (poor B vitamin status) had no benefit at all.[ii] The group with sufficient vitamin B showed a reduction in their clinical dementia score that was more than three times that reported from the recent Lecanemab drug trial.[iii]
Meanwhile another trial, this time in China, gave those with pre-dementia either the B vitamin folic acid, or omega-3, or both, compared to placebo. Although B vitamin treatment and omega-3 treatment did slightly improve cognitive cores, the improvement was much greater in those given both thee nutrients.[iv]
With 170 million people over 65, Chinese authorities are taking prevention of dementia extremely seriously to avoid a cerebral tsunami. So, one of their top researchers, Professor Jin-Tai Yu at Shanghai’s Institute of Neurology at Fudan University did one of the most thorough reviews of all risk factors for Alzheimer’s to date.[v]
“Lowering blood homocysteine levels, an established indicator of Alzheimer’s risk, with B vitamins is a most promising treatment.” he concluded. He was also given access to the UK’s Bio Bank data of almost half a million people “Our current research, using data from the UK Bio Bank, shows that having higher blood levels of polyunsaturated fats, including omega-3, and supplementing fish oils, is associated with less risk of dementia. [vi] Moreover, recent studies suggest these two factors – homocysteine lowering B vitamins, and omega-3 – may, in combination, be potentially more beneficial. They are easy to implement. This is worthy of further research”
The UK’s Bio Bank data showed that something as simple as taking fish oils had reduced dementia risk by 9%. This is equivalent to the risk reduction found from quitting smoking.[vii]
US researchers at the National Institutes of Health research have confirmed this, attributing almost a quarter (22%) of Alzheimer’s cases to lack of B vitamins and raised homocysteine levels and the same (22%) to a lack of omega-3 and seafood intake.[viii] This means that about one in three cases of Alzheimer’s could be avoided simply by taking a daily high dose B vitamin supplement and an omega-3 fish oil capsule. This could save 95,000 people a year in the UK from developing dementia. Currently, 790 people – seven double decker buses worth – are diagnosed every single day. However, the benefit is not just in preventing people from dementia in the future. A study of healthy 65-year-olds given omega-3 fish oils showed both improvement in memory and healthier brain tissue within six months.[ix]
The Alzheimer’s prevention charity, foodforthebrain.org, targets eight prevention steps in their on-line Cognitive Function test and Dementia Risk Index questionnaire, including B vitamins and omega-3. “These are the two easiest to change and most evidence based prevention steps anyone can take.” Say Patrick Holford who directs their ‘Alzheimer’s is Preventable’campaign.
[i] van Soest, A.P.M., van de Rest, O., Witkamp, R.F. et al. DHA status influences effects of B-vitamin supplementation on cognitive ageing: a post-hoc analysis of the B-proof trial. Eur J Nutr (2022). https://doi.org/10.1007/s00394-022-02924-w
[ii] Jernerén F, Cederholm T, Refsum H, Smith AD, Turner C, Palmblad J, Eriksdotter M, Hjorth E, Faxen-Irving G, Wahlund LO, Schultzberg M, Basun H, Freund-Levi Y. Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer’s Disease: The OmegAD Study. J Alzheimers Dis. 2019;69(1):189-197. doi: 10.3233/JAD-181148. PMID: 30958356.
[iii] Walsh S, Merrick R, Richard E, Nurock S, Brayne C. Lecanemab for Alzheimer’s disease. BMJ. 2022 Dec 19;379:o3010. doi: 10.1136/bmj.o3010. PMID: 36535691.
[iv] Li M, Li W, Gao Y, Chen Y, Bai D, Weng J, Du Y, Ma F, Wang X, Liu H, Huang G. Effect of folic acid combined with docosahexaenoic acid intervention on mild cognitive impairment in elderly: a randomized double-blind, placebo-controlled trial. Eur J Nutr. 2021 Jun;60(4):1795-1808. doi: 10.1007/s00394-020-02373-3. Epub 2020 Aug 28. PMID: 32856190.
[v] Yu JT, Xu W, Tan CC, Andrieu S, Suckling J, Evangelou E, Pan A, Zhang C, Jia J, Feng L, Kua EH, Wang YJ, Wang HF, Tan MS, Li JQ, Hou XH, Wan Y, Tan L, Mok V, Tan L, Dong Q, Touchon J, Gauthier S, Aisen PS, Vellas B. Evidence-based prevention of Alzheimer’s disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials. J Neurol Neurosurg Psychiatry. 2020 Nov;91(11):1201-1209. doi: 10.1136/jnnp-2019-321913. Epub 2020 Jul 20. PMID: 32690803; PMCID: PMC7569385.
[vi] Huang Y, Deng Y, Zhang P, Lin J, Guo D, Yang L, Liu D, Xu B, Huang C, Zhang H. Associations of fish oil supplementation with incident dementia: Evidence from the UK Biobank cohort study. Front Neurosci. 2022 Sep 7;16:910977. doi: 10.3389/fnins.2022.910977. PMID: 36161159; PMCID: PMC9489907.
[vii] Jeong SM, Park J, Han K, Yoo J, Yoo JE, Lee CM, Jung W, Lee J, Kim SY, Shin DW. Association of Changes in Smoking Intensity With Risk of Dementia in Korea. JAMA Netw Open. 2023 Jan 3;6(1):e2251506. doi: 10.1001/jamanetworkopen.2022.51506. PMID: 36656579; PMCID: PMC9857334.
[viii] Beydoun MA, Beydoun HA, Gamaldo AA, Teel A, Zonderman AB, Wang Y. Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis. BMC Public Health. 2014 Jun 24;14:643. doi: 10.1186/1471-2458-14-643. PMID: 24962204; PMCID: PMC4099157.
[ix] Witte AV, Kerti L, Hermannstädter HM, Fiebach JB, Schreiber SJ, Schuchardt JP, Hahn A, Flöel A. Long-chain omega-3 fatty acids improve brain function and structure in older adults. Cereb Cortex. 2014 Nov;24(11):3059-68. doi: 10.1093/cercor/bht163. Epub 2013 Jun 24. PMID: 23796946.
Eating a Mediterranean style diet with lots of vegetables and fruit keeps your brain 18 years younger, shows a new study published on the 8th March 2023 in Neurology. According to the researchers “People who scored highest for adhering to the Mediterranean diet had average plaque and tangle amounts in their brains similar to being 18 years younger than people who scored lowest.” They also found people who scored highest for adhering to the MIND diet had average plaque and tangle amounts similar to being 12 years younger than those who scored lowest.”
Adding just one food category from either diet — such as eating recommended amounts of vegetables or fruits — reduced amyloid build-up in the brain to a level similar to being about four years younger, the study said. The greatest result was found with those eating greens. Those in the top third of ‘greens consumption’ had substantially less Alzheimer’s related pathology that those in the lowest third – not eating their greens.
“Doing a simple dietary modification, such as adding more greens, berries, whole grains, olive oil and fish, can actually delay your onset of Alzheimer’s disease or reduce your risk of dementia when you’re growing old,” said study author Puja Agarwal, an assistant professor of internal medicine at the Rush University Medical Center in Chicago.
“Those with a healthy diet have seven times less risk of developing dementia compared to those eating an average diet, according to a study last month in the British Medical Journal” says Patrick Holford, who directs the Alzheimer’s prevention project at Food for the Brain Foundation, “This is completely consistent with Food for the Brain’s free on-line Dementia Risk Index questionnaire which assesses a person’s risk and asks specific questions about diet, including eating greens. Their test includes a Cognitive Function Test which measures actual cognition so you can gauge your brain age. It then advises you what to do to keep your brain young and healthy.”
In the days of Hippocrates, diseases were blamed on the gods. He didn’t buy that and explored the causes of disease saying ‘let food be thy medicine’. Nowadays a lot of diseases are being blamed on genes – because knowledge about genes and their effects has advanced tremendously over the last several decades. Genes are the code, or instructions, to assemble proteins, for example to make an enzyme, a hormone or a biochemical such as cholesterol or phospholipids.
Take Alzheimer’s, which accounts for two thirds of dementia, as an example. There are only three genes that can cause Alzheimer’s (APP, PSEN1, PSEN2), and these account for considerably less than one in a hundred cases of Alzheimer’s. [1]
There are, however, 76 other genes [2] which appear to confer a very small additional risk. Taken together, estimates suggest that 75-85% of the risk can be explained by combining these into a polygenic risk score. [3] The single greatest predictor is the presence of the ApoE4 variant of the ApoE gene, carried by about one in five people. It is considered to contribute 4 to 6% of the absolute risk for Alzheimer’s disease. [4,5]
This is often exaggerated as a risk factor because, if a person has the ApoE4 gene, and changes nothing, they have about a 20% greater chance of developing Alzheimer’s later in life than someone who doesn’t. This is called ‘relative risk’. It doesn’t mean, however, that someone with the ApoE4 gene has a 20% chance of developing Alzheimer’s. This is because, as an example, a person without the ApoE4 gene at a certain age might have a 5% chance of developing Alzheimer’s, while someone with the ApoE4 gene might have a 6% chance, so their risk has gone up by, in this example, 20%. In absolute terms, the risk would be only 1% higher.
Predicting risk and actually reducing risk with modifications of diet and lifestyle are two different things. The predictive risk for Alzheimer’s of having a low intake of seafood and/or omega-3 fats is 22%, and so is having a low intake of B vitamins resulting in a high blood homocysteine level. Smoking confers a similar risk. [6] Other big risk factors are an inactive lifestyle and low level of education. Add in predictive genes and apparent risk adds to well over 100% partly because there is overlap.
But the only way to find out how much you can actually reduce a person’s risk by is to either conduct ‘observational’ studies looking at, e.g. smokers vs non-smokers, or people with a good versus a bad diet, and see how many develop dementia. Even better is to change something, such as looking at what happens when a person stops smoking, or supplements omega-3 fish oils or homocysteine lowering B vitamins.
Modifying ApoE4 with orthomolecular medicine
All these so-called Alzheimer’s genes, with the exception of the causative ones, can only exert effects via non-genetic mechanisms and these mechanisms are often susceptible to modification with a person’s nutrition having the most direct influence. In other words, gene variants that are present are not either active or inactive. Even if you have a gene variant such as ApoE4 it is more like a dimmer switch and can be ‘over-expressed’ or ‘down-regulated’, turned up or dimmed down. That is why approximately half of women with the BRCA gene develop breast cancer and half don’t. The environment the gene is exposed to makes all the difference.
The expression and harmful effects of the ApoE4 gene appear to be downregulated by eating a low-glycemic load (GL) diet or a more ketogenic diet with specific Mediterranean-style food choices including fatty fish, cruciferous vegetables, olive oil, and low alcohol consumption. Six supplemental nutrients have reasonably good evidence of down-regulating ApoE4. These are omega-3 DHA, B vitamins (B2, B6, B12 and folate) vitamins D3 and K2, quercitin and resveratrol. [7] This approach to modifying the effects of the genes we inherit with personalised nutrition is a fundamental tenet of orthomolecular medicine, sometimes called personalised, precision or optimum nutrition.
But what happens to risk if a person is doing these things already? A good example of this is a recent study in China, involving 29,072 people of which 20% had the ApoE4 gene. [8] Each participant had their diet and lifestyle assessed over the 10 year period of the study to see who would or wouldn’t develop cognitive decline or dementia.
The study showed that whether or not a person had the ApoE4 ‘Alzheimer’s gene’ made no difference to the positive reduction in risk achievable by simple diet and lifestyle changes. “These results provide an optimistic outlook, as they suggest that although genetic risk is not modifiable, a combination of more healthy lifestyle factors is associated with a slower rate of memory decline, regardless of the genetic risk,” wrote the study authors.
Eating a healthy diet was the most important prevention step, followed by an active lifestyle, with one’s intellectual life, then physical activity, then social interactions being the next most important steps. Eating a healthy diet was about twice as important as exercise in predicting cognitive decline. Those with a healthy diet were about seven times less likely to have age-related cognitive decline or dementia than those with an ‘average’ diet and about nine times less likely to develop dementia than those with an unfavorable diet.
The assessment of a healthy diet was based on intake of fish, eggs, fruits, vegetables, legumes, nuts and tea, among other foods known to predict lower risk.
B vitamins modify methylation of genes linked to dementia
Other Alzheimer’s related genes affect a process called methylation. Healthy methylation depends on adequate B vitamin intake, primarily B6, B12 and folate. Inheriting a variant of a key methylation gene, MTHFR 677TT increases risk for Alzheimer’s. [9-11] About one in three people have this gene variant. It impacts risk by raising homocysteine, a toxic amino acid that damages the brain and blood vessels. Having a raised homocysteine level increases risk for cerebrovascular dysfunction 17-fold. [12]
Since methylation is needed to make phospholipids, biochemicals essential for the brain also found in eggs and fish, having a poor diet in this respect creates more methylation demand and, consequently, greater need for B vitamins.
In a placebo controlled study of older people with mild cognitive impairment, about a third of participants had the MTHFR variant that increases Alzheimer’s risk. But supplementing with B vitamins effectively lowered homocysteine in both those with and without this ‘Alzheimer’s’ gene. The B vitamin supplement almost arrested further memory decline and slowed the rate of brain shrinkage by 52%, [13,14] reducing shrinkage of the Alzheimer’s areas of the brain by 9-fold. [15] Whether a person did or didn’t have this ‘Alzheimer’s’ gene made no difference to the beneficial effect of the B vitamins.
Those with adequate omega-3 blood levels had even less brain shrinkage – 73% less than the placebo group. [16-17] Two other studies have found major protection either by giving B vitamins to those with adequate omega-3 intake, [18] or by supplementing omega-3 to those with lower homocysteine levels [19] further confirming that you need both B vitamins and omega-3 fats to keep neurons healthy – an example of synergy – regardless of one’s genes. Whether a person did or didn’t have the MTHFR variant made no significant difference.
Too often genes are blamed as drivers of disease even though (with the exception of rare causative genes) the primary drivers are what you put in your mouth or how you live your life – both factors under our control. For example, DNA genetic testing can cause panic when an individual is informed they have a dozen or more gene variants. Over-emphazing the importance of genes discourages people from preventing their own disease by improving diet and lifestyle.
Find out your dementia risk
Cognitive Function Test Results
You can find out what’s driving your risk and which diet and lifestyle changes will make the biggest difference by doing the Cognitive Function Test at foodforthebrain.org and joining COGNITION, the brain upgrade program. Not only do you help yourself, you also help the hundreds of thousands of people who would benefit from the research we support at Food for the Brain to reduce risk of dementia.
About Patrick Holford
(Patrick Holford , BSc, DipION, FBANT, NTCRP is widely published and a member of the Orthomolecular Medicine Hall of Fame. He is the director of the non-profit, UK-based “Alzheimer’s is Preventable” campaign [ foodforthebrain.org].)
2. Bellenguez C, Küçük F, Jansen IE, et al. (2022) New insights into the genetic etiology of Alzheimer-s disease and related dementias. Nat Genet. 54:412-436. https://pubmed.ncbi.nlm.nih.gov/35379992
3. Escott-Price V, Myers AJ, Huentelman M, Hardy J. (2017) Polygenic risk score analysis of pathologically confirmed Alzheimer disease. Ann Neurol. 82:311-314. https://pubmed.ncbi.nlm.nih.gov/28727176
4. Heininger K (2000), A unifying hypothesis of Alzheimer’s disease. III. Risk factors. Hum Psychopharmacol Clin Exp. 15:1-70. https://pubmed.ncbi.nlm.nih.gov/12404343
6. Beydoun MA, Beydoun HA, Gamaldo AA, et al. (2014) Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis. BMC Public Health. 14:643. https://pubmed.ncbi.nlm.nih.gov/24962204
7. Norwitz NG, Saif N, Ariza I.E, Isaacson RS (2021) Precision Nutrition for Alzheimer’s Prevention in ApoE4 Carriers. Nutrients 13:1362. https://pubmed.ncbi.nlm.nih.gov/33921683
8. Jia J, Zhao T, Liu Z et al. (2023) Association between healthy lifestyle and memory decline in older adults: 10 year, population based, prospective cohort study. BMJ 380:e072691. https://pubmed.ncbi.nlm.nih.gov/36696990
9. Morris AA, Kožich V, Santra S, et al. (2017) Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency. J Inherit Metab Dis. 40:49-74. https://pubmed.ncbi.nlm.nih.gov/27778219
10. Bouguerra K, Tazir M, Melouli H, Khelil M. (2022) The methylenetetrahydrofolate reductase C677T and A1298C genetic polymorphisms and plasma homocysteine in Alzheimer’s disease in an Algerian population. Int J Neurosci. 29:1-6. https://pubmed.ncbi.nlm.nih.gov/36580407
11. Zuin M, Cervellati C, Trentini A, et al. (2021) Methylenetetrahydrofolate reductase C667T polymorphism and susceptibility to late-onset Alzheimer’s disease in the Italian population. Minerva Med. 112:365-371. https://pubmed.ncbi.nlm.nih.gov/32700867
12. Teng Z, Feng J, Liu R, et al. (2022) Cerebral small vessel disease mediates the association between homocysteine and cognitive function. Front. Aging Neurosci. 14:868777. https://pubmed.ncbi.nlm.nih.gov/35912072
13. Smith AD, Smith SM, de Jager CA, et al. (2010) Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One. 5(9):e12244. https://pubmed.ncbi.nlm.nih.gov/20838622
15. Douaud G, Refsum H, de Jager CA, et al. (2013) Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. Proc Natl Acad Sci USA 110:9523-9528. https://pubmed.ncbi.nlm.nih.gov/23690582
16. Jernerén F, Elshorbagy AK, Oulhaj A, et al. (2015) Brain atrophy in cognitively impaired elderly: the importance of long-chain omega-3 fatty acids and B vitamin status in a randomized controlled trial. Am J Clin Nutr. 102:215-221. https://pubmed.ncbi.nlm.nih.gov/25877495
17. Oulhaj A, Jernerén F, Refsum H, et al. (2016) Omega-3 fatty acid status enhances the prevention of cognitive decline by B vitamins in Mild Cognitive Impairment. J Alzheimer’s Dis. 50:547-557. https://pubmed.ncbi.nlm.nih.gov/26757190
18. van Soest, A.P.M., van de Rest, O., Witkamp, R.F. et al. (2022) DHA status influences effects of B-vitamin supplementation on cognitive ageing: a post-hoc analysis of the B-proof trial. Eur J Nutr. 61:3731-3739. https://pubmed.ncbi.nlm.nih.gov/35704085
19. Jernerén F, Cederholm T, Refsum H, et al. (2019) Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer’s Disease: The OmegAD Study. J Alzheimers Dis. 69:189-197. https://pubmed.ncbi.nlm.nih.gov/30958356
One theory was that it was to do with the accumulation of amyloid protein, producing amyloid plaque that interferes with brain cell communication. But, despite over 30 clinical trials, lowering amyloid protein has had close to zero clinical effect. But, even if this was part of the problem, one would have to ask why?
There are plenty of left-field theories. One, for example, is that it’s an auto-immune disease whereby the brain starts to destroy itself. There are plenty of diet and lifestyle diseases that tip over into auto-immune diseases. For example, type-2 diabetes can convert to type-1 diabetes and osteoarthritis can convert to rheumatoid arthritis. But even so, one would have to ask why? What would be driving this?
Risk Factors for Alzheimer’s – what do they have in common?
There are over 20 known risk factors that predict future risk for cognitive decline, dementia and/or Alzheimer’s. These include:
Anon-adherence to Mediterranean diet principles
Cardiovascular disease, and high blood pressure
Depression/social isolation/loneliness
Diabetes
Genes (such as senilin) and predisposing genes (eg ApoE4)
Head trauma
High blood homocysteine (a measure of B vitamins)
Insulin resistance
Lack of antioxidants/polyphenols in plant foods
Lack of cognitive stimulation
Lack of exercise and muscle mass – frailty
Lack of folate, B12 and B6
Lack of sleep
Low education level
Low phospholipid and choline intake (in eggs and fish)
Low seafood consumption and a lack of omega-3
Low sunlight exposure
Low vitamin C, D and E intake
Low zinc levels
Medication – antiacids, metformin, diuretics
Metabolic syndrome
Poor gut health and dental health
Poor hearing
Smoking
Stress
Strokes and TIAs (transient ischemic attacks )
Too much sugar, refined, processed, carb-rich foods
So far researchers have looked at individual known risk factors for Alzheimer’s, then tried to change them with some success. The nutritionists have tried to change diet, or give supplements. The pharmacologists have tried to give drugs to lower, for example, high blood pressure or insulin levels. The psychologists have tried to increase cognitive stimulation and address depression and isolation, and insomnia. The sports physiologists have tried to increase exercise. But what do all these factors have in common? Is there a way of looking that ties all these risk factors together into an understanding as to what is actually driving dementia?
The old, but still dominant mindset in science is ‘reductionism’. The idea is to look at one thing, or one risk factor, then change it in a randomised placebo-controlled trial. The idea is that if everyone does this then you could pool all the interventions together to produce a cure. This reminds me of a comment made in the G8 summit on dementia in 2010, in London, when we succeeded in getting a discussion on dementia prevention added to the agenda. The pharma representative said words to the effect of ‘we will solve dementia with multiple drugs, just like we solved AIDS’. The reality is studies giving drugs[1] to lower blood sugar for diabetics, lower blood pressure with anti-hypertensive drugs, lower cholesterol with statins, even lower amyloid protein, have failed. The official cost of all this research is $42.5 billion to date.[2] This is five times more than the cost of the James Webb telescope. This approach clearly isn’t working. The only ‘drugs’ that have worked are homocysteine lowering B vitamins and omega-3 fish oils – and the recent discovery is that they work together, in cooperation.
There’s a new emerging way of doing science which is called ‘systems-based’ science. The physicist, Fritjof Capra, has explained this way of doing science in his book ‘The Web of Life’. He says “Systems thinking emerged from a series of interdisciplinary dialogues among biologists, psychologists, and ecologists, in the 1920s and ’30s. In all these fields, scientists realized that a living system—organism, ecosystem, or social system—is an integrated whole whose properties cannot be reduced to those of smaller parts. The “systemic” properties are properties of the whole, which none of its parts have. So, systems thinking involves a shift of perspective from the parts to the whole. The early systems thinkers coined the phrase, “The whole is more than the sum of its parts.”[3]
Us humans are a complex adaptive system. What’s also been learnt about complex adaptive systems is that they have a certain amount of ‘resilience’ which you can think of as the credit in your health deposit account. When that runs out, disease occurs. Many leaders in the field of nutritional and naturopathic medicine consider that many of the same underlying processes are going wrong in our bodies, which then cause the emergence of a ‘disease’ depending on the organ it strikes – so heart disease, diabetes, arthritis and dementia have similar contributing factors.
At Food for the Brain, we can organise all these risks above into eight domains shown below. It is certainly true that these eight domains of ‘risk’ cover much of what we know about the risks for heart disease, diabetes and arthritis, for example. This partly, but not fully. answers the question about what is actually driving dementia.
The Eight Domains of Dementia Risk
Another understanding within systems-based thinking is well illustrated by asking the question ‘what is the difference between an inanimate object, like a bicycle, and an animate organism, such as us?’ A bicycle has ‘parts’ and the parts related to each other, as in functioning together. So do we. But also, there is ‘life’ running through us. You can imagine your brain’s neural network lighting up, with ‘energy’ or signals shooting this way and that. If you have healthy parts, all functioning, but no signals, you’re kind of ‘switched off’.
We call the parts – structure; the relationship of the parts – function; and the life running through the neural network – utilisation. These are shown visually below in a way to illustrate that they are integral, with each dependent on the other.
Now, let’s reorganise all those risk factors accordingly into whether they are primarily required for the structure or function of the neural network, or send messages across it.
Protecting the Structure of Your Brain
If you’ve watched the short animated film ‘how to keep building brain cells at any age‘ you’ll know that the membrane of every brain cell is made by binding omega-3 DHA, rich in seafood, to phospholipids and especially Phosphatidylcholine, rich in eggs and fish, to produce what called ‘phosphorylated DHA’. You need this to have a functioning brain. It actually makes up more than 90 per cent of the structure of your brain.
You’ll also know that the ‘binding’ of these two parts depends on B vitamins, which drive a process called methylation. So, without enough B vitamins your brain and nervous system fall apart. The best measure of methylation, and whether you are getting enough B vitamins, is your blood homocysteine level. If your homocysteine level is high, you’ve got a problem. Above 11mcmol/l and you’ve got a shrinking brain. More than half of all people over 70 have a homocysteine level above this. It should, therefore, be no surprise to find that, if you have a raised homocysteine level, and are given B vitamins, if you also have a low omega-3 DHA intake or blood level, the B vitamins won’t work. Conversely, if you supplement omega-3 fish oils, but have a raised homocysteine level or lack of B vitamins, the omega-3 won’t work. The full story of the dynamic duo of Omega-3 and B vitamins is explained here.
It is likely that choline deficiency, which is especially common in those who rarely eat fish or eggs, may also create a similar structural problem in the brain. In animals supplementing choline prevents Alzheimer’s related brain changes.[4]
Protecting the Function of Your Brain
There are many aspects of ‘function’ of the brain. Using a simple car analogy, one thinks of the need for fuel and the need for oil to lubricate the parts. The two main fuels of brain cells are either glucose, derived from carbs, or ketone derived from fat.
If you’ve watched the animated film ‘how to fuel your brain for better memory’, you’ll know about the need for slow-releasing carbs and ketones from a type of fat called a medium chain triglyceride (MCT) and specifically C8 oil.
Too much sugar, and especially fructose and high fructose corn syrup (now used by the food industry to sweeten foods), and too much refined carbohydrates interferes with fuel supply to brain cells by making you ‘insulin resistant’. Insulin receptors, embedded in neuronal membranes, transport glucose into brain cells. If these receptors, which are like doors, are largely shut down, the brain starves of clean fuel. Read professor Robert Lustig’s article “Is sugar killing your brain?’ for the full story.
The alternative brain fuel – ketones, which neurons actually prefer, can be made in the liver from a type of fat called C-8 (caprylic acid triglyceride) which makes up 7 per cent of coconut oil. In a study giving people with memory problems two tablespoons of C8 oil, their brains produced 230 per cent more energy from ketones and their memory improved. The article ‘Is fat the best brain fuel?’ gives you the full story.
The lubricating ‘oil’ in a car analogy would be both dealing with the ‘exhaust fumes’ of the brain’s energy production, namely oxidants. These are mopped up by antioxidants and polyphenols rich in plant foods. That where food such as blueberries and cacao, or vitamin C and E, come in. It’s also why smoking is such a big risk factor.
Another part of ‘function’ is circulation – anything that improves circulation helps the function. Many of the things we’ve mentioned – lowering homocysteine with B vitamins, omega-3, antioxidants, polyphenols – also help circulation.
Another part of ‘function’ is inflammation. Behind all those ‘metabolic’ diseases -diabetes, heart disease, arthritis to name a few – lies inflammation which doesn’t just affect the specific organ, be it heart of joint, but also the brain.
Use it or Loss it – Why Your Brain Needs Stimulation
One of our experts, Tommy Wood, assistant research professor at the University of Washington in Seattle, focussing on neuroscience, has developed an excellent model for understanding the ‘use it or lose it’ principle. He’s big into exercise.
‘Exercise is important because it makes the brain do things that keep it healthy, such as growth and repair and maintaining temperature and weight,’ he says. ‘When they aren’t stimulated, the health of brain tissues deteriorates with a knock-on effect on memory and thinking.’
And it’s not just physical exercise that does this, we also benefit from the mental exercise involved in likes of solving puzzles or learning a new language. ‘For many people the worst thing they can do for their brain is to retire’, says Wood. ‘They lose much of the stimulation that kept it healthy.’
Sleep as a brain protector also fits in here. It’s vital for recovering from both physical and intellectual exercise and to store and organise what you have learnt in the day.
‘But sleep and exercise aren’t enough on their own,’ Wood continues. ‘All that repair and maintenance needs a good supply of nutrients.’
Taken from J.Turknett & T.Wood, Cells 2022, 11, 2789, used with permission.
Stress also fits in here because stress, as well as environmental and dietary ‘pollution’ be it from drinking and smoking, dirty air, moulds, even allergens like gluten with can induce ‘brain fog’ often experienced by those with coeliac disease, promote inflammation and inhibit repair and regeneration.
A Unified Model for the Drivers of Cognitive Decline
This systems-based approach to what’s potentially driving cognitive decline makes it obvious that there will never be a single drug or single factor that stops a person developing dementia. Instead, if a person has enough ‘interference’ with the structure, function or utilisation of their brain then there will, inevitably be cognitive decline with age.
At Food for the Brain, when you complete your Cognitive Function Test, you know objectively how you are doing and how much room for improvement there is. Then you are invited to complete the Dementia Risk Index questionnaire, which not only gives you a score out of 100% (you are aiming for a score closer to 0%) but also shows you in which domain you have the most room for improvement.
Cognitive Function Test Dashboard
You are then invited to join COGNITION, which is an interactive brain upgrade programme that targets your weakest areas and shows you the simplest changes that will make the biggest difference to reduce your risk.
The goal is to turn all your reds, oranges and yellows into green, then reassess your cognitive function. By joining you are becoming part of a group of hundreds of thousands of citizen health scientists helping to discover what really works to dementia-proof your diet and lifestyle.
[1] Peters R, Breitner J, James S, Jicha GA, Meyer PF, Richards M, Smith AD, Yassine HN, Abner E, Hainsworth AH, Kehoe PG, Beckett N, Weber C, Anderson C, Anstey KJ, Dodge HH. Dementia risk reduction: why haven’t the pharmacological risk reduction trials worked? An in-depth exploration of seven established risk factors. Alzheimers Dement (N Y). 2021 Dec 8;7(1):e12202. doi: 10.1002/trc2.12202. PMID: 34934803; PMCID: PMC8655351.
[2] Cummings JL, Goldman DP, Simmons-Stern NR, Ponton E. The costs of developing treatments for Alzheimer’s disease: A retrospective exploration. Alzheimers Dement. 2022 Mar;18(3):469-477. doi: 10.1002/alz.12450. Epub 2021 Sep 28. PMID: 34581499; PMCID: PMC8940715.
[3] Fritjof Capra (2009) The New Facts of Life: Connecting the Dots on Food, Health, and the Environment, Public Library Quarterly, 28:3, 242-248, DOI: 10.1080/01616840903110107
[4] Velazquez R, Ferreira E, Knowles S, Fux C, Rodin A, Winslow W, Oddo S. Lifelong choline supplementation ameliorates Alzheimer’s disease pathology and associated cognitive deficits by attenuating microglia activation. Aging Cell. 2019 Dec;18(6):e13037. doi: 10.1111/acel.13037. Epub 2019 Sep 27. PMID: 31560162; PMCID: PMC6826123.
A recent study of 1,178 women found that those carrying the APOE4 gene taking Hormone Replacement Therapy (HRT) had a better delayed memory score compared to APOE4 carriers that were not taking HRT, and to non-APOE4 carriers.[1] They also had slightly larger brain volumes in certain areas. This study suggested that HRT may help to prevent Dementia. This study was an observational trial, not a clinical trial, meaning the statement remains a hypotheses and requires further randomised controlled trials to investigate further. We analysed the paper and provided our comments below.
Hormone Replacement Therapy (HRT) are synthetic hormones commonly prescribed to menopausal women to reduce menopausal symptoms
Clinical Trials on HRT
Clinical trials to date have not shown benefit of HRT with improving cognitive function. A systematic review of the clinical trial evidence for the effect of HRT on cognitive outcomes did not find benefit.[2] The Women’s Health Initiative Memory Study (WHIMS) conducted a double-blind, placebo-controlled clinical trial examining 8300 women 65 years of age or older over a 2- year period to observe the effects of HRTs and dementia progression. The trial failed to find a beneficial effect for HRT in reducing dementia risk, instead finding an increase in all types of dementia.[3]
The ApoE4 Gene
Roughly 1 in 5 people carry the ApoE4 gene, which accounts for 4 to 6% of risk for dementia and can be modified, downregulating the gene, with positive diet, nutritional supplement and lifestyle changes.[1]
Find out your risk for Dementia
In our Dementia Risk Index, as part of the Cognitive Function test, and COGNITION programme to reduce dementia, we excluded HRT because the evidence was not conclusive or consistent.
Have you tried our free Cognitive Function Test yet? Find out your Alzheimer’s disease risk using our evidence backed Dementia Risk Index. If your risk is high, our clever new programme COGNITION can help you make the right nutrition and lifestyle changes to help improve your score.
The 8 Domains of the Dementia Risk Index from The Cognitive Function Test
References
[1] Saleh RNM, Hornberger M, Ritchie CW, Minihane AM. Hormone replacement therapy is associated with improved cognition and larger brain volumes in at-risk APOE4 women: results from the European Prevention of Alzheimer’s Disease (EPAD) cohort. Alzheimers Res Ther. 2023 Jan 9;15(1):10. doi: 10.1186/s13195-022-01121-5. PMID: 36624497; PMCID: PMC9830747.
[2] Marjoribanks J, Farquhar C, Roberts H, Lethaby A, Lee J. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2017;1(1):CD004143.
[3] Shumaker SA, Legault C, Rapp SR, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in post- menopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003;289(20):2651-2662.
What makes us humans so different to other apes is our larger brain, especially the cortex. It is three times larger than a chimpanzee. How did this happen? How did Homo Sapiens evolve our level of intelligence despite sharing almost the same genes?
The brain’s origin, for all species, is from the ocean. It had to be as that is where life began. Millions of years ago the rudimentary eye cell, dinoflagellate, which is a type or marine phytoplankton, used a specific fat – the omega-3 fat docosahexanoic acid (DHA) – to convert solar photon energy into the first nerve impulse or twitch – a twitch towards food. That is the origin of the nervous system and brain.
Back in the ‘80’s, when zoologist Professor Michael Crawford analysed the types of fat in different animal’s organs and muscles they varied according to their dietary environment, except the brain. He discovered that the brain is always rich in DHA. The more DHA the brighter the animal, with the sea mammals and us humans having exceptionally high levels.
Recently it has been proven that DHA (docosahexanoic acid) has a unique structure involving six double bonds, arranged in a horseshoe shape, which actually makes it a semi-conductor with unique electrical properties. Its close cousins, ALA (alpha linolenic acid) in chia or flax, and EPA (eicosapentanoic acid) don’t have this potential. It’s all about DHA. While some EPA converts into DHA less than 1 per cent of ALA in plant-based sources of omega-3 such as chia seeds converts to DHA, the richest source of which is marine-based food from rivers and the sea.
Over 6 million years ago our hominid ancestors split from other apes (chimps, gorillas and bonobos), culminating in Homo Sapiens around 100,000 years ago. It clearly wasn’t genes that made us different. We share 98.5% of the same genome. It had to be the environment our ancestors exploited. During this time brain size steadily increased up to 1.45kg 10,000 years ago, roughly three times the size of a chimpanzee, at 384g.
Homo Aquaticus
We have over twenty profound anatomical, physiological and biochemical differences apart from our vastly different psychological advancement as in intelligence and language. More than anything, it is this, illustrated by our brain size, that makes us different. But, before looking closely at the circumstances, and diet, that almost certainly drove our gain in brain size and intelligence, let’s take a look at the fundamental differences we have. These have been so clearly delineated in an excellent book, The Waterside Ape, by Peter Rhys-Evans, and ear, nose and throat surgeon. He explores why we:
Stand upright
Have (virtually) no body hair
Have a layer of sub-cutaneous fat
A waxy, waterproof layer, the vernix, at birth
A diving reflex at birth, meaning we are able to swim before we can walk, and hold our breath underwater
A descended larynx, a precursor of being able to have complex language/speaking
Enlarged sinus cavities
A nose shape that is good for keeping the water out while swimming
Ears that actually form a protective boney protusion in those who spend a lot of time diving
Different kidneys, in how they filter salt and water
Manual dexterity
Crinkly fingers when in water for a few minutes
Of course, the story we’ve all been told is that we came out of the trees, into the savannah and stood upright for better hunting. Anyone who has been on safari will know that a) you don’t stand a chance catching anything by standing upright – you crawl; and b) all the good hunters can sprint much faster than man (lion 80kph, leopard 60kph, cheetah 100kph, man under 30kph) precisely because four legs are better than two. But, can you explain any one of these other changes, let alone our increase in intelligence, by moving from the trees into the savannah for hunting? If so, how did we suddenly develop manual dexterity, tools and spears overnight to even survive? Also, why do certain ‘sea nomad’ tribes exist, such as the Moken and Bajou, who can hold their breath for up to 10 minutes under water, spending up to five hours a day in the sea, giving birth in the sea? Their spleen is adapted to oxygenate tissue, as it is in dolphins, to enable long dives. Where did that evolutionary adaptation come from?
The only logical explanation that I have encountered, which eloquently fits all these adaptations, in that our hominid ancestors exploited the waterside – wetlands, swamplands, rivers, estuaries and coasts. In the process of so doing, became upright, and started to eat a diet high in marine foods, providing the essential nutrients for brain development, that is omega-3 DHA, phospholipids, plus vitamin B12, iodine, and all those other essential elements from magnesium to selenium. From this perspective let’s briefly examine all the changes listed above, between us and other apes:
Stand upright – better for wading in water, so gradually our anatomy adapts but, even so, we are prone to the problems of uprightness, eg hips and knees because it is anatomically inferior to walk on all fours, with better weight distribution.
Have (virtually) no body hair and a layer of sub-cutaneous fat – consistent with semi-aquatic mammals better for floating and insulation
A waxy, waterproof layer, the vernix, at birth – found in no land mammals, only other semi-aquatic mammals such as seals and chemically identical
A diving reflex at birth, meaning we are able to swim before we can walk, and hold our breath underwater
A descended larynx, a precursor of being able to have complex language/speaking – being upright, and diving, could have led to this vital adaptation. This, by the way, only occurs after a year or so, before which a baby’s language cannot develop the complexity of sounds and voice control only we have
Enlarged sinus cavities, which help to keep the head above water, but still have drainage holes in the ‘wrong’ place, eg good if on all fours but bad if upright, which is why we are prone to sinus problems.
A nose shape that is good for keeping the water out while swimming
Ears that actually form a protective boney protusion in those who spend a lot of time diving
Manual dexterity – if we were wading, and swimming, not walking on all fours, we have ‘free’ hands. Opening shells would develop manual dexterity.
Crinkly fingers when in water for a few minutes – perfect for catching fish.
Part of the idea of the ‘savannah’ theory is that food became scarce with climate changes so we switched to hunting. But the water’s edge was, until recently, abundant with easily accessible food. Even 200 years ago, in 1706, Daniel Dafoe wrote this regarding the Firth of Forth. “Off the Pentland Firth the sea was one third water and two thirds fish; the operation of taking them could hardly be call’d fishing, for they did little more than dip for them into the water and take them up.” Our estuaries were packed with mussels, oysters and crabs.
Historically, wherever early man is found so too is evidence of seafood consumption, with remains of shells, fish bones etc. from Pinnacle Point in South Africa, where early remains are found together with sea shells, to Wales. When a 40,000 year old Homo sapiens was found in the Gower peninsular DNA evidence showed that a quarter of their diet was seafood.
A marine food diet high in critical brain building nutrients, especially DHA, phospholipids and B12, is the best explanation for our cerebral expansion. “Docosahexaenoic acid (DHA), the omega-3 fatty acid that is found in large amounts in seafood, boosts brain growth in mammals. That is why a dolphin has a much bigger brain than a zebra, though they have roughly the same body sizes. The dolphin has a diet rich in DHA. The crucial point is that without a high DHA diet from seafood we could not have developed our big brains. We got smart from eating fish and living in water.” says Crawford.
The dry weight of the brain in 60 per cent fat and DHA makes up over 90 per cent of the structural fat of neurons (brain and nerve cells). The intelligent membrane that makes up all neurons is composed of phosphorylated DHA – that is DHA attached to phospholipids. The most abundant phospholipid is phosphatidyl choline, found predominantly in fish, eggs and organ meats. These are bound together by a process called methylation, itself dependent on vitamins B12, folate and B6. While folate and B6 is found in both plant foods and seafood, B12 is only found in foods of animal origin, and is especially high in all marine foods.
The evidence that exists suggests we were eating a diet rich in marine food, as well as plant foods along the water’s edge, enjoying the ‘fruité del mare’. We would have eaten much more than we do today – at least double the calories. Today’s convenience world has dramatically reduced the calories we need to expend hunting and gathering food, travelling and staying warm.
The idea that we were eating twice as much and at least a quarter from marine foods makes sense of what we know about the optimal intake of both omega-3 fats rich in DHA, phospholipids and vitamin B12, lack of which are the main drivers of today’s endemic dementia. This would be equivalent to at least half our diet today needing to be from marine foods rich in fats.
Optimal amounts of omega-3 from seafood is estimated at 2 grams a day by Joseph Hibbeln at the US National Institute’s of Health, while choline is estimated at 400mg to 800mg. An optimal intake of B12 is probably 10mcg. None of these can easily be achieved even by eating seven servings of oily fish a day. (Choline is rich in all fish, but DHA is only rich in oily fish, fish roe and liver.)
In the chart below the last column combines EPA and DHA and shows the amount provided in an 85g serving. None provide 2,000mg, although they do get close, suggesting that we would have needed to eat at least a serving of fish or seafood a day, if not more.
Fish and Seafood (per 85g)
EPAmg
DHAmg
EPA+DHAmg
Atlantic Salmon (farmed)
587
1238
1825
Atlantic Herring
773
939
1712
Atlantic Salmon (wild)
349
1215
1564
Bluefin Tuna
309
970
1279
Mackerel (canned)
369
677
1046
Sockeye Salmon (wild)
451
595
1046
Rainbow Trout (farmed)
284
697
981
Sardines (canned)
402
433
835
Albacore (or white) Tuna (canned)
198
535
733
Shark (raw)
267
444
711
Swordfish
117
579
696
Sea Bass
175
473
648
Pollock
77
383
460
Flat Fish (Flounder/Sole)
207
219
426
Halibut
77
318
395
Oysters (farmed)
195
179
374
Dungeness Crab
239
96
335
Scallops
141
169
310
Mixed Shrimp
145
122
267
Clams
117
124
241
Yellowfin Tuna
40
197
237
Catfish (wild)
85
116
201
Catfish (farmed)
42
109
151
Cod
3
131
134
Mahi-Mahi (dolphin fish)
22
96
118
Tilapia
4
111
115
Brain size remains reasonably constant from 100,000 to 10,000 years ago, then starts to shrink, perhaps coinciding with the birth of agriculture and diets based more on meat, milk and plants than marine foods. Today, average brain size is 1.35kg.
The evolution of intelligence and self-awareness
Apart from brain size and, more pertinently, brain to body size ratio, what sets us apart from other animals is self-awareness. Animals have the equivalent of thoughts and feelings but humans are relatively unique in being able to witness one’s own thoughts and feelings, that is self- awareness. This is not an easy thing to measure, but some other mammals, notably dolphins, gorillas and chimpanzees, also have a degree of self-awareness. Other contenders for higher cognition include octopuses and elephants, all large brained creatures. However, it isn’t just size that counts. In essence, there are three evolutions of the brain. First, the reptilian brain located on the brain stem, which programmes basic survival needs. Then there’s the mammalian brain, with more cognitive and emotive functions (think dog), then the neo-cortex, associated with higher cognition. But, while elephants have larger brains they have smaller neo-cortexes. It’s the neo-cortex that starts to grow in our hominid ancestors.
An indication of an advancing intelligence could be supposed from the earliest evidence of ancient rock art, as well as use of complex tools and adornments. The earliest rock art is found in South Africa, dating back 77,000 years ago, and in Western Europe about 37,000 years ago, and possibly in Australasia (Sulawesi) around that time.
The richest concentration of ancient rock art over 6,000 years ago, however, is found in sub-Saharan Africa, the Nile Valley and Red Sea hills, then a green belt with vast lakes, rivers and wetlands, hence abundant marine foods, which lasted until about 3,500 years ago when much of Egypt is becoming a desert. Whether the drying up of the Sahara was linked to the Younger Dryas (see below), a change in the Earth’s tilt or over grazing is a subject of debate.[i]
Meanwhile, groups of our early ancestors who had left Africa, living in Europe as far west as Ireland, north as Scandinavia, East as China and Australia, were also struck by cataclysmic weather changes. In Europe the Magdalenian culture, with advanced stonework, exists from 17,000 years ago, coinciding with the end of the Ice Age, until 12,000 years ago, coinciding with the Younger Dryas, a period of extreme cooling which lasted for circa 1,000 years, possibly triggered by a meteor shower[i]. One theory has ancestors migrating south, towards warmer climates with available water, possibly carrying with them the sticky grains they had previously gathered, and may have planted them in moist soil as a means to survive, thus giving birth to the agricultural age whereby mankind moves away from a hunter gatherer lifestyle towards an agricultural lifestyle. This also makes sense as these two pockets of humanity, in Mesopotamia (now Iraq), between the Tigris and Euphrates river, and Egypt, becoming more densely populated with the need for stored food, supplied by grains and domesticating animals. This stable food supply would have allowed expansion of these populations. (There is another evolutionary hotspot in Asia and China[i].)
Early Enlightenment
The likely existence of an ‘enlightened’ culture, Atlantis, is eluded to in the writings of Plato, possibly existing around the fertile region of the then much smaller Black Sea, which is thought to have flooded across the Bosphorus peninsular when the Mediterranean sea levels rose to a critical mass, dated back to around 7,000 years ago. This may also be the origin of the Flood myth, which occurs in ancient Sumerian lore dating back 5,000 years and later Hebrew lore.
Thus we have this triangle between the Black Sea to the North, Egypt to the South, and Mesopotamia to the East, all with evidence of evolved culture, including monotheism. The Sumerian culture appears over 6,000 years ago in the fertile crescent of Mesopotamia. Later, circa 2,500 years ago, we have the enlightened Zoroastra in Mesopotamia forming the Parsi culture in what is now Iran. Also,The Aryan-(Dru)Vedic culture, sometimes located east of the Black sea, migrated into the Indus valley in northern India as the main influence of the now Hindu culture, and the start of the Greek culture, considered to be the origin of our Western culture. The earliest hint of a Druidic culture dates back to this time. One stream of ancient druidic lore talks of a cataclysmic event, stones pouring from the sky, raising the possibility that early stone structures and barrows were built effectively as ‘bomb shelters’.[i] While the meaning of the word ‘dru’ is associated with oak (those who meet by the oak) and truth, it also may also mean worshippers of the red Sun (du rua). Sun and fire worship is shared by the early Egyptians (Ra), (dru)vedic culture (Agni and Surya), Zoroastrian culture(Mithra) and even Sumerian culture (Utu). The use of fire started much earlier, with it’s discovery a million years ago, and widespread use from 500,000 years ago, which expanded humanity’s ability to derive energy from previously indigestible carbohydrates, as evidenced in the DNA with the emergence of multiple variations in carbohydrate- digesting amylase enzymes. This is also linked to an expansion in brain size.[ii]
Is Homo Sapiens devolving?
Globally, there is an increase in mental illness which is fast becoming the biggest health threat, according to the World Health Organisation. There is also evidence that our brain size has reduced by 10 per cent, from 1.45kg 10,000 years ago[1] to an average now of 1.35kg, coinciding with a more land-based food supply. According to Scandinavian research, our IQ is also falling by 7 per cent a generation. Global rates of depression and dementia, suicide and stress-related disorders of anxiety and insomnia are escalating. One in six children in the UK are classified with ‘special educational needs’ (SEN). Suicide, globally, has become the most cause of violent deaths, ahead of all wars and murders. In the UK 790 people a day, nine double decker buses worth, are diagnosed with dementia. Global incidence will top 100 million this decade, already costing over 1% of GDP.
On the assumption that our brains still require at least the same supply of nutrients that our semi-aquatic ancestors were able to eat during the period of maximum brain evolution – although one could argue that the digital age has put more stress on our brain function, hence we might even need more nutrients – and the fact that we are simply not achieving anything like the same intake of the brain’s essential fats, phospholipids and micronutrients, is it any wonder that mental health is in sharp decline? With a growing population and declining available seafood, coupled with contamination with heavy metals, PCBs and micro-plastic particles, matters are likely to get much worse.
High sugar intake, in animals, has been shown to lead to shrinking of the brain’s hippocampal region. This is where the nucleus accumbens, the seat of the brain’s dopamine-based ‘reward’ system, stimulated by sugar, caffeine and tech addiction, (especially that based on variable rewards such as the ‘like’ button) resides. Marketeers have learnt how to create addiction to their products by stimulating the reward system, selling short-term pleasure, the dopamine-based feeling, in the guise of happiness. The happy hour, the happy meal, happiness in a bottle etc. Over-stimulation of the reward system ultimately leads to dopamine depletion and brain cell death, coupled with a decline in serotonin, the tryptamine associated with happiness, connection, love, empathy and other essential qualities of a harmonious society – and the very qualities that make us human.
We are therefore witnessing the devolution of the brain, the decline and fall of mental health and harmonious society, a situation that is likely to get worse as population expands, unless we rapidly find a way to optimally nourish the brain.
Building Healthy Brains
The emphasis in human nutrition has, for too long, been on the body. With more protein, meat and dairy products, we have grown taller, but not smarter. As director of the Institute of Brain Chemistry at the Chelsea and Westminster Hospital, Professor Michael Crawford has been able to accurate predict which pregnant women are most likely to have pre-term babies, with an increased risk of cognitive delay or impairment. This is based on determining the supply, by analysing the pregnant woman’s blood, of DHA. In its absence levels of a surrogate fat, oleic acid, rises to fulfil the requirement of the neonatal brain, when DHA is in short supply. It is, however, an inadequate substitute and thus cognitive development is impaired. Babies born of mothers with low blood DHA levels, compared to those supplementing DHA, have smaller brains.[2]
According to Crawford, with a growing population and shrinking fish supply, we must develop marine agriculture on a massive scale to survive and protect the brain. In the same way that man moved from hunter gatherer on the land to peasant farmer, we too must move from hunter gatherer in the oceans to marine farmer. In Japan he has been instrumental to the creation of artificial reefs in the estuaries to attract back the marine food web, from mussels to crustaceans, and fish, as well as farming seaweed on a massive scale. By processing seaweed it is possible to create DHA, the critical brain fat that is crucially lacking in a plant-based diet. As Crawford says “We now face a world in which sources of DHA – our fish stocks – are threatened. That has crucial consequences for our species. Without plentiful DHA, we face a future of increased mental illness and intellectual deterioration. We need to face up to that urgently.”
At the other end of the lifecycle, more and more older people are slipping into dementia, which is a preventable but not reversible condition. At the University of Oxford, Professor David Smith has shown that inadequate omega-3 fats (DHA and EPA) and B vitamins, especially vitamin B12, are the principle drivers of cognitive decline. Yet, by providing these nutrients to those with pre-dementia, further memory decline and brain shrinkage can be arrested. B12 is only found in animal foods and is especially rich in seafood. A plant-based diet alone does not provide sufficient DHA, B12 or phospholipids require for optimal brain development.
Therefore, it is vital that the needs for optimal brain function are put at the top of the health agenda to prevent the decline of our mental health and potentially the fall of Homo Sapiens. Without our fully functioning brains humanity will neither have the insight nor cooperation to face and resolve the challenges we face with a growing population, reducing food supply, increasing pollution, climate changes and ever-increasing energy demands.
Food for the Brain is a non-for-profit educational and research charity that offers a freeCognitive Function Testand assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.
By completing theCognitive Function Testyou are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.
Brain Fats – Seafood, Omega-3 PUFAs, Phospholipids and Vitamin D
The omega-3 fat, docosahexaenoic acid (DHA) is the most abundant PUFA in the brain, concentrated in the grey matter and, particularly at the synapses.1 DHA is incorporated into membrane phospholipids, where it affects the properties of the membrane, for example, maintaining membrane fluidity. DHA, along with other omega-3 fats EPA, DPAn-3 and their mediators are involved in a wide variety of processes in the brain, such as making new neurons, synaptic connections and the regulation of inflammation.2
Fish, especially cold-water oily fish, contain high levels of DHA and EPA, and epidemiological studies consistently suggest that an elevated fish intake is associated with decreased risk of neurodegenerative diseases, such as Alzheimer’s disease.3 Recent estimates suggest that worldwide many populations are currently consuming DHA and EPA at levels well below the recommendations issued by many international authorities (GOED), with and blood levels of EPA and DHA have been estimated to be low to very low for most of the world, which may increase global risk for chronic disease.4
Interestingly, positive associations have also been found between walnut consumption and cognitive performance.5 Walnuts are a source of omega-3 fat, alpha-linolenic acid (ALA) and also a range of antioxidants.
Omega-3 Supplementation and cognitive decline
DHA supplementation appears to show the greatest promise in the early stage before the onset of memory loss symptoms,1 and at levels at or above 1000 mg per day (Ismail 2015).6
A study of healthy 50-75 year olds were given 2,200 mg a day of omega 3 fish oils for six months not only reported significant increase in executive function, one aspect of cognition that is a hallmark of Alzheimer’s, but also beneficial structural changes in white matter integrity and grey matter volume in the brain. The cognitive improvement correlated with blood levels of omega-3 PUFAs.7
A randomized, double-blind, placebo-controlled, clinical study, gave 900 mg of DHA a day for 24 weeks and reported an improvement in learning and memory function in those with age-related cognitive decline.8 In a further trial by the same research group, giving 2,000 mg a day of DHA or placebo to 402 people with mild to moderate Alzheimer’s disease, therefore further along the disease process, for a period of 18 months found no cognitive improvement.9
Phospholipids
Phospholipids, rich in eggs and seafood, are abundant in the brain. They make up the membranes of the different types of cells in the brain. These include Phosphatidylethanolamine (PE) and phosphatidylserine (PS) phosphatidylcholine (PC) and phosphatidylinositol (PI). They become attached to omega-3 DHA. (see film ‘Build Your Brain‘) Phosphatidylethanolamine (PE) and phosphatidylserine (PS) are enriched in DHA, whereas much lower levels are found in phosphatidylcholine (PC) and phosphatidylinositol (PI).3 Attaching DHA to phospholipids is a process that requires methylation, which is dependent on B vitamins.9 Interestingly, although DHA is typically found high in PS, levels have been found to be low in PS in post-mortem samples from Alzheimer’s disease patients.10 PS supplementation may benefit cognition in the elderly,11 but as PS is highly enriched with DHA, it is currently unclear whether the potential beneficial effects of PS on cognition are due to the intact PS or DHA. Although PC is not highly enriched in DHA, higher plasma concentrations of PC-DHA are associated with reduced risk of dementia and AD,12 and post mortem samples from AD shows depletion of PC-DHA in grey matter.13
Supplementation
A number of trials have investigated the effects of providing multinutrient supplements containing a range of nutritional factors with the aim of supporting phospholipid biosynthesis. Our recent systematic review identified that omega-3 PUFAs and B vitamins as part of these multinutrient formulas confers benefits on cognition in older adults across a range of different types of measures of cognition in older adults.14 Furthermore, 12-week trial of citicoline has shown cognitive benefits in healthy older adults.15
Vitamin D
The primary source of vitamin D is exposure to sunlight. Seafood provides the most dietary vitamin D. Vitamin D deficiency increases risk of AD.161,17,18 Supplements of vitamin D can be derived from animal or fungal sources (mushrooms and yeast). Supplementing 800iu (20mg) a day for 12 months has been shown to improve cognitive function and lessen amyloid protein markers.19
In a study in France involving 912 elderly patients followed for twelve years, a total of 177 dementia cases (124 AD) occurred: 25(OH)D deficiency was associated with a nearly three-fold increased risk of AD.20
References
1.Dyall, S. C. (2015, 2015-April-21). Long-chain omega-3 fatty acids and the brain: A review of the independent and shared effects of EPA, DPA and DHA [Review]. Frontiers in Aging Neuroscience, 7(52). https://doi.org/10.3389/fnagi.2015.00052
2. Dyall, S. C., Balas, L., Bazan, N. G., Brenna, J. T., Chiang, N., da Costa Souza, F., Dalli, J., Durand, T., Galano, J. M., Lein, P. J., Serhan, C. N., & Taha, A. Y. (2022, Apr). Polyunsaturated fatty acids and fatty acid-derived lipid mediators: Recent advances in the understanding of their biosynthesis, structures, and functions. Prog Lipid Res, 86, 101165. https://doi.org/10.1016/j.plipres.2022.101165
4. Stark, K. D., Van Elswyk, M. E., Higgins, M. R., Weatherford, C. A., & Salem, N., Jr. (2016, Jul). Global survey of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults. Prog Lipid Res, 63, 132-152. https://doi.org/S0163-7827(15)30033-3 [pii]10.1016/j.plipres.2016.05.001 Alzheimers Dement. 2017 Nov;13(11):1207-1216. doi: 10.1016/j.jalz.2017.03.003. Epub 2017 May 16
5. Theodore LE, Kellow NJ, McNeil EA, Close EO, Coad EG, Cardoso BR. Nut Consumption for Cognitive Performance: A Systematic Review. Adv Nutr. 2021 Jun 1;12(3):777-792. doi: 10.1093/advances/nmaa153. PMID: 33330927; PMCID: PMC8166568.
6. Ismail
7. A. Veronica Witte, Lucia Kerti, Henrike M. Hermannstädter, Jochen B. Fiebach, Stephan J. Schreiber, Jan Philipp Schuchardt, Andreas Hahn, Agnes Flöel, Long-Chain Omega-3 Fatty Acids Improve Brain Function and Structure in Older Adults, Cerebral Cortex, Volume 24, Issue 11, November 2014, Pages 3059–3068, https://doi.org/10.1093/cercor/bht163
8. Yurko-Mauro K, McCarthy D, Rom D, et al; Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement. 2010; 6, 456-64
9. Quinn JF, Raman R, Thomas RG, et al; Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA, 2010; Nov 3;304(17):1903-11.
10. A David Smith, Fredrik Jernerén, Helga Refsum, ω-3 fatty acids and their interactions, The American Journal of Clinical Nutrition, Volume 113, Issue 4, April 2021, Pages 775–778, https://doi.org/10.1093/ajcn/nqab013
11. Cunnane, Stephen & Schneider, Julie & Tangney, Christine & Tremblay-Mercier, Jennifer & Fortier, Mélanie & Bennett, David & Morris, Martha. (2012). Plasma and Brain Fatty Acid Profiles in Mild Cognitive Impairment and Alzheimer’s Disease. Journal of Alzheimer’s disease : JAD. 29. 691-7. 10.3233/JAD-2012-110629.
12. Richter Y, Herzog Y, Lifshitz Y, Hayun R, Zchut S. The effect of soybean-derived phosphatidylserine on cognitive performance in elderly with subjective memory complaints: a pilot study. Clin Interv Aging. 2013;8:557-63. doi: 10.2147/CIA.S40348. Epub 2013 May 21. PMID: 23723695; PMCID: PMC3665496.
13. Schaefer EJ, Bongard V, Beiser AS, Lamon-Fava S, Robins SJ, Au R, Tucker KL, Kyle DJ, Wilson PW, Wolf PA. Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study. Arch Neurol. 2006 Nov;63(11):1545-50. doi: 10.1001/archneur.63.11.1545. PMID: 17101822.
14. Yuki D, Sugiura Y, Zaima N, Akatsu H, Takei S, Yao I, Maesako M, Kinoshita A, Yamamoto T, Kon R, Sugiyama K, Setou M. DHA-PC and PSD-95 decrease after loss of synaptophysin and before neuronal loss in patients with Alzheimer’s disease. Sci Rep. 2014 Nov 20;4:7130. doi: 10.1038/srep07130. PMID: 25410733; PMCID: PMC5382699.
15. Fairbairn, P., Dyall, S. C., & Tsofliou, F. (2022, Apr 27). The Effects of Multi-Nutrient Formulas containing a Combination of Omega-3 Polyunsaturated Fatty Acids and B vitamins on Cognition in the older adult: A Systematic Review and Meta-analysis. Br J Nutr, 1-42. https://doi.org/10.1017/S0007114522001283
16. Nakazaki E, Mah E, Sanoshy K, Citrolo D, Watanabe F. Citicoline and Memory Function in Healthy Older Adults: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J Nutr. 2021 Aug 7;151(8):2153-2160. doi: 10.1093/jn/nxab119. PMID: 33978188; PMCID: PMC8349115.
17. Sommer I, Griebler U, Kien C, Auer S, Klerings I, Hammer R, Holzer P, Gartlehner G. Vitamin D deficiency as a risk factor for dementia: a systematic review and meta-analysis. BMC Geriatr. 2017 Jan 13;17(1):16. doi: 10.1186/s12877-016-0405-0. PMID: 28086755; PMCID: PMC5237198;
18. Jayedi A, Rashidy-Pour A, Shab-Bidar S. Vitamin D status and risk of dementia and Alzheimer’s disease: A meta-analysis of dose-response †. Nutr Neurosci. 2019 Nov;22(11):750-759. doi: 10.1080/1028415X.2018.1436639. Epub 2018 Feb 15. PMID: 29447107;
19. Chai B, Gao F, Wu R, Dong T, Gu C, Lin Q, Zhang Y. Vitamin D deficiency as a risk factor for dementia and Alzheimer’s disease: an updated meta-analysis. BMC Neurol. 2019 Nov 13;19(1):284. doi: 10.1186/s12883-019-1500-6. PMID: 31722673; PMCID: PMC6854782.
20. Jia J, Hu J, Huo X, Miao R, Zhang Y, Ma F. Effects of vitamin D supplementation on cognitive function and blood Aβ-related biomarkers in older adults with Alzheimer’s disease: a randomised, double-blind, placebo-controlled trial. J Neurol Neurosurg Psychiatry. 2019 Dec;90(12):1347-1352. doi: 10.1136/jnnp-2018-320199. Epub 2019 Jul 11. PMID: 31296588.
21. Feart C, Helmer C, Merle B, Herrmann FR, Annweiler C, Dartigues JF, Delcourt C, Samieri C. Associations of lower vitamin D concentrations with cognitive decline and long-term risk of dementia and Alzheimer’s disease in older adults. Alzheimers Dement. 2017 Nov;13(11):1207-1216. doi: 10.1016/j.jalz.2017.03.003. Epub 2017 May 16. PMID: 28522216.
Robert Lustig is Professor Emeritus of Pediatrics in the Division of Endocrinology, and Member of the Institute for Health Policy Studies at the University of California, San Francisco. He is a pediatric neuroendocrinologist,and an international authority on obesity, diabetes,nutrition,and neuroscience. He is the author of three books that have changed our understanding of the danger of sugar on our metabolism – Fat Chance, The Hacking of the American Mind, and Metabolical.
Most people know that refined sugar is not good for you, but what is it about sugar that’s particularly bad for your brain? Why is it essential, not only for brain health and dementia prevention, to reduce your intake of not only sugar but refined carbohydrates in general? (By refined, I mean those whose fiber has been processed away – not ‘whole’ as in vegetables, whole fruit (not juice), beans, and whole grains.
Let’s start at the extreme. What happens if you lived at the North Pole, and ate virtually no carbohydrates, or at least so little as to force your body and brain to switch to a kind of fuel, ketones, produced from fat? This is often called a “very low carb high fat” (LCHF) or “ketogenic” diet. Would you get sick? This is what Vilhjamur Steffanson did, when his Arctic exploration shipwrecked in 1913, and he was forced to live amongst the Inuit for two years. He noted that there was no diabetes, no cancer — and no Alzheimer’s. In 1928, he and his colleague checked themselves into Bellvue hospital, and ate only meat for one year.[1]They were healthier than the researchers who studied them!
Your brain likes ketones
Ketones are made in the liver from fat – either breaking down your own fat (for example, if you were fasting, eating very little or exercising a lot), or from ingestion of a type of fat containing ‘medium chain triglycerides’ (MCTs). Coconut oil is approximately 54% MCTs and contains all 4 MCTs (C6, C8, C10, C12), but it turns out that one particular kind of MCT, called C8 because it is 8 carbons long, is the best fat for the liver to convert into ketones.
You may be surprised to know that your brain can run well on glucose (the kind of sugar that is fuel for our cells), but even better on ketones. The reason is that ketones cross into the brain easily, rapidly, and without a biochemical transporter. This is why children with severe epilepsy improve on a ketogenic diet. Watch this short film ‘Fuel your Brain’.
Brain benefits of a low-carb ketogenic diet
In fact, brain cells prefer ketones. In two studies, one on people with Alzheimer’s and the other on those with pre-dementia or mild cognitive impairment, giving 2 tablespoons of C8 oil (called capricin or caprylic acid triglyceride), brain energy derived from ketones went up by 230% and memory and mental acuity improved in those with Minimal Cognitive Impairment (MCI).[2,3]
A ketogenic diet has been shown to reduce schizophrenia symptoms, help reduce shaking in Parkinson’s, and slow down cognitive decline in those with dementia or pre-dementia. In fact, the ketogenic diet has been used to effectively treat childhood epilepsy for over 100 years! There’s a good review on the current status of the ketogenic diet in psychiatry here.[4]
Ketogenic diets may help in many ways. Firstly, when a person eats too much carbohydrate, sugar, but especially fructose, damages the energy burning factories in cells, called mitochondria, so their ability to produce chemical energy for the neuron is greatly reduced. Switching to burning ketones instead can increase mitochondria number and function. A recent study also shows that a ketogenic diet has a positive effect on the gut microbiome,[5] and this might be one way the diet helps reduce fits in people with epilepsy.[6] Fructose, on the other hand, disrupts the gut microbiome in a negative way.
How sugar damages your brain
But what is it about a ketogenic diet that is good for your brain? Is it the ketones, the lowering of insulin, the type of fat, the elimination of carbohydrate, or specifically the elimination of sugar? We don’t yet know – I ask this question of every Alzheimer’s and metabolic researcher I know, and no one can tell me – just that it works.
There are a few possible mechanisms. First, the more carbs and sugar you eat, the more resistant you become to the hormone insulin. Insulin not only drives glucose into cells (including brain cells), but also sends excess sugar to the liver to turn into fat. When a person becomes insulin resistant, ironically, glucose transport is negatively impacted, reducing brain energy availability. Insulin resistance is a major driver of depression.[7] A ketogenic diet can reverse that.
Fructose, which comprises half of sucrose (‘white’ or ‘table’ sugar), and half of ‘high-fructose corn syrup’ (added to numerous processed foods), damages our mitochondria, which leads to less brain energy availability. One study showed that fructose reduces liver mitochondrial function, while glucose stimulates it.[8]“The most important takeaway of this study is that high fructose in the diet is bad,” said Dr. C. Ronald Kahn from the Joslin Diabetes Center. “It’s not bad because it’s more calories, but because it has effects on liver metabolism to make it worse at burning fat. As a result, adding fructose to the diet makes the liver store more fat, and this is bad for the liver and bad for whole body metabolism.”
Fructose is the main sugar in most fruits. People then extrapolate, “oh fruit must be bad for you.” Not true. Whole fruit has fibre (both soluble and insoluble); together they slow down glucose and fructose absorption in the GI tract limiting both liver and brain exposure, and they also help feed the gut bacteria (microbiome), so actually you get less fructose entering the bloodstream. Juicing the fruit removes the protective fiber, and juice has been shown to be just as dangerous to metabolism as is soda. So, eat your fruit — don’t drink it!
Carbohydrates and fructose age your brain
There’s another reason why sugar, and especially fructose, is bad for your brain and body. They produce Advanced Glycation Endpoints or AGEs, which damage the brain. These ‘oxidise’ proteins (so does cigarette smoke), rendering them useless , allowing them to aggregate into clumps, and use up valuable antioxidants in your diet such as vitamin C and E.
Fructose acts on your liver to switch your metabolism away from fat burning to fat making and storing, and inhibits an anti-ageing process called ‘autophagy’ which helps clean up and remove damaged mitochondria in order to regenerate new, healthier cells.
Why sweet foods are so addictive
So far we’ve only explored why sugar is bad for your “physical” brain. Knowing this is a good start. But why does your “emotional” brain keep telling you that you want it? Why do people find it so hard to resist, and so many become sugar addicts? The answer is that fructose activates the “reward system” in the brain. It causes dopamine release, the motivational neurotransmitter associated with ‘reward’. Any chemical that does so can be addictive – cocaine, heroin, alcohol, nicotine, or example. The trouble is the more you have, the more your brain ‘down-regulates’, i.e. becomes less responsive to your own natural feel-good dopamine, so you end up needing more sugar to get the hit and, in the end, you get no hit at all but feel thoroughly awful without it. That’s the Law of Diminishing Returns. That’s addiction.
Blood sugar control reduces dementia risk
Keeping blood glucose levels in the low-normal range is reflected by a low blood glycosylated haemoglobin (HbA1C) level, which means ‘sugar-coated red blood cells’. A low HbA1c is good and is a proxy for improved insulin sensitivity, associated with reduced risk for dementia in several studies.[9,10,11,12,13,14]
A new study also shows that, in 40 year old adults with so-called normal glucose levels but at the higher end of the normal range, have increased their risk of Alzheimer’s by 15% [37]
Type 2 diabetes, the net result of losing blood sugar control, almost doubles the risk for dementia.[15,16] Diabetes is also associated with more rapid brain shrinkage.[17,18] Even people in the upper normal range of blood glucose have increased brain atrophy, impaired cognition, and increased risk of dementia.[19,20]
For instance, one trial measured HbA1c and glucose levels in several thousand elderly people over the course of almost seven years.In that time, slightly more than a quarter of the participants developed dementia, and the bottom line was that rising glucose levels were associated with increased risk of developing the condition, irrespective of whether the participants also had diabetes. Non-diabetics who experienced a modest increase in blood sugar levels had an 18% increased risk of dementia, as compared to those who already had diabetes at the start of the study or developed it within the trial period, who had a 40% increased risk.[21]
Insulin resistance is strongly related to cognitive decline
But even more important than loss of glucose control is the loss of insulin control. Back in 2004, researchers at Columbia University showed that people with high insulin levels – the principal hallmark of metabolic dysfunction – were twice as likely to develop dementia as those with healthy levels. Moreover, those with the highest insulin levels had the worst memory retrieval.[22] The same year, an Italian study established a link between heightened insulin levels and declining mental function.[23] Similarly, a Puerto Rican study found that people who consumed the large amounts of sugar doubled their risk of suffering poor cognitive function,[24] while another US study discovered a strong correlation between blood sugar level and memory loss.[25]
Two studies – one in Ireland,[26] and the other in the United States,[27] – established a link between high dietary glycemic load (GL; how high does your blood glucose rise when you eat carbohydrate) and cognitive decline. Indeed, both of these reports suggested that high GL is even more predictive of the pathological changes associated with Alzheimer’s than either high carb or high sugar intake. A high GL diet is also associated with more amyloid plaque[28] and more cognitive decline, especially in those who carry the ApoE4 gene, a regulator of fat metabolism.[29]
A long-term study found evidence that this sort of shrinkage is more common among people with high blood glucose levels, even when those levels are still within what are considered ‘normal’ (i.e. non-diabetic) limits.[30] This cognitive decline starts young. Cognitive decline in overweight children is associated with a high GL diet[31], and adolescents with metabolic dysfunction driven by a high GL diet have been shown to have shrinkage of the hippocampal area of the brain, as well as other structural changes and cognitive deficits. [32,33]
Prevention action – how to cut down your sugar load
In practical terms, preventing dementia today means avoiding sugar as much as possible. If you’re going to eat carbohydrate, eat ‘whole’ carbohydrate foods such as whole vegetables, fruits (not juice), beans, only wholegrain bread (labelled as ‘100% wholegrain’, or pasta in small quantities.
Starchy carbohydrates such as pasta, rice and potatoes benefit from being cooked and cooled, then eaten cold or re-heated, as some of the carbohydrate is converted into resistant starch – a type of fibre we can’t digest but which has the added benefit of fermenting and feeding our gut bacteria.
Make sure the carbohydrate comes with its inherent fibre. Oat cakes would be better than bread since the fibre in these foods helps ‘slow release’ the sugars. Eating white bread is associated with a poorer cognitive test performance, whereas high fibre bread is associated with better performance.[34] Eating carbohydrate foods with protein, for example brown rice with fish, or porridge oats with seeds, or fruit with nuts, further reduces the glycemic load (GL) of a meal. The best fruits in this respect are low-sugar high-fiber fruits like berries, cherries, and plums.
These kinds of foods are consistent with a Mediterranean diet which has also been shown to reduce risk.[35] Conversely, grapes, raisins, and bananas are high GL. A study in Finland and Sweden compared those with a healthy versus unhealthy diet, including the above criteria, in mid-life for future risk of developing Alzheimer’s disease and dementia 14 years later. Those who ate the healthiest diet had an 88% decreased risk of developing dementia and a 92% decreased risk of developing Alzheimer’s disease.[36]
The take-home message is, if you are going to eat complex carbohydrates, eat them with fibre, fat and protein.
However, if you want to go one step further, you can switch to eating a ketogenic low-carb, high fat diet. The problem with the ketogenic diet is staying on it – there’s so much carbohydrate out there it’s hard to avoid it. But there are now breath monitors (e.g. Ketoscan, BioSense from ReadOut Health) that can help you stay in ketosis. A good book to help you explore and put into practice either a low carb ketogenic diet or a low GL diet is ‘The Hybrid Diet’ by Patrick Holford & Jerome Burne. And to understand how processed food is your enemy, take a look at my book ‘Metabolical’.
And if you want to know how sugar is impacting your body and brain then upi can take one of our at-home, pin-prick, HbA1c (sugar) blood test so you can know exactly how sugar is impacting your body and also become apart of our vital research into this area.
Food for the Brain is a non-for-profit educational and research charity that offers a freeCognitive Function Testand assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.
By completing theCognitive Function Testyou are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices
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