The Alzheimer’s Prevention Expert Group have accused The Lancet journal of "bad science" and knowingly ignoring two highly effective and firmly evidence-based ways to reduce risk factors for dementia.
Patrick Holford heads up the APEG, a collaboration of renowned scientists focused on preventing cognitive decline.
The group claims The Lancet report on dementia downplays the role nutrition plays in modifying the risk.
The report, released in July, identified 14 modifiable risk factors that could prevent around 45 per cent of dementia cases.
It added two new risk factors: untreated vision loss and high LDL cholesterol.
The other risk factors they cite include:
- Education
- Hypertension
- Physical inactivity
- Diabetes Social isolation
- Excessive alcohol consumption
- Air pollution
- Smoking
- Obesity
- Traumatic brain injury
- Depression
The Lancet Commission on dementia was convened to review the best available evidence and produce recommendations on how to best manage, or even prevent, the dementia epidemic.
"The question is: 'What is actionable that could reduce the risk of dementia, which is a massive cost?" Mr Holford asked rhetorically, adding that he struggles to see how air pollution fits into this equation.
"How are you going to change your air pollution because it's adding two per cent to the risk of dementia? The answer is you can do nothing about it all so it's not very actionable," the nutrition expert continued.
He points out there's not a single randomised control study on air pollution, only observational studies.
RCTs compare the effectiveness of different treatments or interventions by randomly assigning participants to two groups:
- Experimental group: Receives the intervention being tested
- Control group: Receives an alternative intervention, a placebo, or no intervention at all
Observational studies are a lower standard of evidence than experimental studies, more prone to bias and confounding, and cannot be used to demonstrate causality.
The absence of widespread randomised controlled trials (RCTs) on air pollution can be attributed to numerous ethical, logistical, and practical challenges.
For example, you'd have to deliberately expose one group to a potential hazard while protecting another and the sheer logistical complexity of controlling exposure levels over extended periods, which is nearly impossible outside of highly controlled environments.
In contrast, supplementing with high-dose supplements of B vitamins and omega-3 fish oils is an actionable step is both cost-effective and backed by "overwhelming" evidence, Mr Holford claims.
The APEG is also trying to get the journal to recognise the benefits of a low-sugar diet, although they appreciate this is less "cut and dry".
Let's take a closer look at each claim.
The scientists are baffled by the inclusion of air pollution, which is less robustly supported than the supplements
Getty ImagesB vitamins
The single most effective evidence-based intervention is lowering homocysteine with B vitamins, the scientists say.
Homocysteine is a toxic amino acid that accumulates when there is a lack of B vitamins in your body. It damages your brain as well as your arteries.
A high homocysteine level is a biomarker for over 100 diseases, especially those of the central nervous system.
For example, it's a biomarker of impaired cognitive abilities in children and adults, and for stroke, dementia and Alzheimer’s, but also possibly for depression, anxiety, bipolar, schizophrenia, obsessive-compulsive disorder, Parkinson’s and multiple sclerosis.
A raised homocysteine level therefore means something is going wrong with a vital process that controls how we think, feel and perceive.
And it's entirely dependent on B vitamins.
Some people absorb B12 less well. Others need more of the B vitamin than others and that biochemical individuality, especially if their diet is already deficient, "can tip them into a mental or neurological illness", explains Mr Holford.
Indeed, "it is very much the forgotten factor, and is easily corrected", explained pharmacology professor David Smith, formerly Deputy Head of the Faculty of Medical Sciences at the University of Oxford and member of the APEG.
The best evidence of the cognitive benefits of B vitamins comes from a meta-analysis published in the British Medical Journal.
The systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials concluded that lowering homocysteine with B vitamins is the most promising intervention preventing Alzheimer's disease.
Last month a review in the Journal of Prevention of Alzheimer’s Disease listed reducing homocysteine among the top five evidence-based actions.
A US National Institutes of Health review attributes almost a quarter (22 per cent) of the risk of Alzheimer’s to raised homocysteine and a further 22 per cent to lack of seafood and omega-3 fish oils.
Omega-3
The combined effect of omega-3 and B vitamins is greater than either nutrient on its own, research suggests.
Oxford University researchers recently revisited a study on people with pre-dementia and looked at the blood levels of omega-3 at the start of the study.
They were not given omega-3. They were given B vitamins or a placebo, and they found something unique. Those with low omega-3 status have no benefit from the B vitamins.
Yet those with high omega-3 status had 73 per cent less brain shrinkage.
It may be possible to prevent up to 80 per cent of dementia cases if all known risk factors, including homocysteine-lowering B vitamins and omega-3, found in oily fish, were targeted, reckons Professor Yu of Fudan Univeristy in Shanghai, who is also a member of the APEG.
Another meta-analysis of 14 studies published in the British Journal of Nutrition found those aged 60-70 who supplemented with a combination of B vitamins and omega-3 fats had less cognitive decline than those who did not.
The research, which included a total of 4913 people who were followed up between six months and four years concluded: “Increasing intake of both nutrients benefits cognition in older adults compared to placebo."
Vitamin D deficiency has also been linked to cognitive decline.
For example, a large-scale study supported by the National Institute for Health and Care Research (NIHR) Exeter Biomedical Research Centre found that taking vitamin D was associated with living dementia-free for longer, and they also found 40 per cent fewer dementia diagnoses in the group who took supplements.
A prospective cohort study of 12,388 participants found that those who were exposed to vitamin D had a 40 per cent lower risk of developing dementia.
The study also found that the effects of vitamin D were more pronounced in women, people with normal cognition, and people who were not carriers of the apolipoprotein E ε4 gene - a risk factor for Alzheimer's disease.
The combination of high homocysteine, low omega-3 and vitamin D is present in the majority of those over 50 and quadruple dementia risk, according to research published this year in The American Journal of Clinical Nutrition.
“Remarkably, a suboptimal status of all three nutrients was associated with a four-fold increased risk of dementia,” said lead author Professor Annick van Soest at Wageningen University,
Professor Jin-Tai Yu, co-author of a study in the journal Nature, together with Professor Smith analysed data from the UK Biobank which concluded that "up to 73 per cent of dementia cases can be prevented”.
However, this may be a conservative estimate as this study excluded blood test measures, notes Professor Smith.
He added: “This figure could be higher if a person’s omega-3 and B vitamin status, measured, by a blood test for homocysteine were taken into account.”
Furthermore, studies in Holland, Norway, the UK and China have additionally reported a synergistic effect between B vitamins and omega-3, with several times better clinical benefit than any dementia drug.
A study at Oxford University showed two-thirds less brain shrinkage in those with mild cognitive impairment when given B vitamins with sufficient omega-3, compared to placebo.
And one-third of trial participants were clinically dementia-free at the end of one year.
The dementia prevention charity foodforthebrain.org, which tests homocysteine, omega-3 and vitamin D blood levels, attributes 35 per cent of modifiable risk to a deficiency of B vitamins and brain fats.
Mr Holford acknowledges the limitations to the role deficiencies play in cognitive decline, namely, it's a sliding scale.
For example, one study participant can have more or less deficiency than another. It's hard to control these confounding variables but the research still is relatively "straightforward", the nutrition expert says.
The combined effect of omega-3 and B vitamins is greater than either nutrient on its own, researchers say
Getty Images
Low sugar
Less straightforward is the role sugar plays in the development of dementia.
According to Mr Holford, the best way to measure the impact of sugar on the brain is to look at ultra-processed foods, which contain eight times more added sugars than processed foods and five times more than unprocessed or minimally processed foods.
Research has shown that the more ultra-processed foods a person eats, the more their brain shrinks and the greater their risk of dementia.
Studies have found that diets low in nutrient-dense foods can decrease thev volume of the hippocampus, the part of the brain that's important for learning and memory.
Mr Holford acknowledges that it's hard to isolate sugar as the contributing factor but the evidence does support this hypothesis.
The association is more indirect but the evidence is accumulating. He cites studies in children and teenagers with metabolic syndrome - a cluster of conditions that occur together, increasing your risk of heart disease, stroke and type 2 diabetes. A diet high in sugar can increase the risk of metabolic syndrome
These study participants showed brain shrinkage in certain areas and worse cognitive function.
For example, a review of the literature published in the American Heart Association concluded adolescents who had metabolic syndrome risk factors had volume losses in the hippocampus and frontal lobe.
The hippocampus and frontal lobe are two brain regions that work together to support learning, memory, and other cognitive functions.
Objectively measuring what constitutes high or low sugar is another challenge, Mr Holford notes, although you can measure blood glucose.
In one study, scientists determined that people who have a raised blood glucose in midlife increase their risk of Alzheimer's later on by 15 per cent.
Research also shows that a high HPA1C - the standard measure doctors use for diagnosing diabetes - increases the risk of dementia too.
When someone eats too much sugar, they become insulin resistant.
Insulin is a hormone that drives glucose into the brain. It's the "delivery system", Mr Holford explains. It also regulates the amount of glucose in your blood.
Eating too much sugar can cause your pancreas to produce too much insulin, which can lead to insulin resistance over time. This is where your body becomes less responsive to insulin.
This means your blood glucose goes up as normally insulin would take glucose out of the blood and transport it to the muscles and brain.
As a result, glucose hangs about in the blood instead.
This means glucose does not get it into the brain. So the irony of too much sugar is you end up "sugar starved", Holford explains.
"The consequence of that is brain fog, cognitive decline and neuronal death," he warned.
Fructose - a naturally occurring sugar that is found in fruits, vegetables, honey, and sugar cane - is also a "toxin" to the brain, Mr Holford continues.
Evidence supports his claims.
For example, a study published in The American Journal of Clinical Nutrition suggests that fructose metabolism may trigger a survival response that could lead to Alzheimer's disease.
Another study from the Framingham Heart Study found that higher fructose consumption was associated with an increased risk of dementia and Alzheimer's disease.
Sugar is a "major player" but it's harder to measure than B vitamins and B vitamins and omega-3, Mr Holford and his colleagues tell GB News.
Higher fructose consumption is associated with an increased risk of dementia and Alzheimer's disease
Getty ImagesAnyone there?
The combined deficiencies of homocysteine, omega-3 and vitamin D - so easily corrected - could have a bigger impact on dementia risk than any of the 14 risk factors listed in The Lancet Commission’s report, the scientists claim.
The APEG has repeatedly flagged this with the Lancet Commission but they have heard nothing.
The normal process is that if you write a paper and you get it published in the Lancet or another journal and somebody wishes to object or make a point, they write to the Lancet.
The letter will then be subject to peer review. If it meets the requirements, this letter will be published.
The APEG has submitted three letters to the Lancet Commission for peer review since its first report in 2017 but they haven't had them published.
GB News has seen these three letters. The three letters submitted to the Lancet on omega-3, homocysteine and fructose/sugar, listing the authors, can be viewed here.
The normal process is that if you write a paper and get it published in The Lancet and somebody wishes to object or make a point, they write to the Lancet. I am sent the letter. They publish the letter and as author, they publish my reply.
Despite being sent all the evidence and the three letters, the report’s scientists, headed by UCL Professor Gill Livingston, have "ignored it", Mr Holford claims.
Asked why she continued to deny any benefit from homocysteine lowering Professor Gill Livingston allegedly told the group of scientists: “High homocysteine only affects a small number or people and there are no trials that show that lowering it has any benefit.”
When approached for comment, Professor Livingston told GB News: "I am not in charge of publishing letters in the Lancet – that is the editorial team. I have not heard from The Lancet about these letters.
"Our commission (attached) has put together the best evidence we can with a group of international experts and have been transparent about how we did it. The work has been peer-reviewed. We do not dismiss the evidence about food but explain why it is not strong or specific enough. The extensively referenced section on diet is in the attached paper."
She also provided the conclusion of this report, which read:
"In conclusion, nutritional epidemiology studies often, but inconsistently, report an association between diet and biomarkers, cognitive decline, dementia, or Alzheimer’s disease. Studies are of few diets and mostly focus on those in high-income countries, consisting of Mediterranean or similar diets, which are rich in vegetables, nuts, berries, beans, seafood, and whole grains. Clinical trials have generally reported that nutritional and dietary interventions do not reduce cognitive impairment. Intervention results are small, heterogeneous, usually not significant, and could be considered hypothesis-generating at best but do not support the primary hypotheses. Positive results in some subgroups indicate that future investigation might be useful and that long-term interventions might be needed to show an effect. Eating a diet high in fruit and vegetables and low in ultra-processed foods is good for many health conditions and affects the dementia risk factors of obesity, diabetes, and hypertension, but insufficient evidence exists to say that this diet is directly useful for dementia prevention.”
This is simply not true, the scientists counter.
In its place, two far less significant risk factors have been added to The Lancet report - cholesterol and cataracts, they say.
The report claims cataract surgery would eliminate two per cent of overall risk.
The report cites follow-up studies in the US, which found that those who had cataract extractions had significantly reduced risk for dementia — a 29 per cent decrease — as opposed to those who did not have cataract extractions.
In contrast, reducing high homocysteine, which affects about one in two of over 65 could potentially eliminate a quarter of all risk, “saving the UK economy approximately £60 million per year”, according to Oxford University health economist, Professor Apostolos Tsiachristas.
The commission has also ignored studies showing a benefit from improving omega-3 status by eating fish or taking supplements, the AGPR notes.
The Lancet Report cited only one study linking higher blood levels of omega-3 fatty acids with risk for dementia which concluded that this study provided “compelling evidence for a relationship between long-chain omega-3 fatty acids levels and lower risks for dementia and related outcomes”.
It would have been "so easy" for the Lancet Commission to search the meta-analyses on omega-3 in public databases yet they chose to focus on study, Mr Holford said.
What's more, essentially the same conclusions were reached by at least eight other similar studies.
“Why were these studies ignored?” asked Professor William Harris of the Fatty Acid Research Institute, a leading omega-3 expert in the US.
“The vast majority of adults in the western world have suboptimal blood omega-3 fatty acid levels. Increased consumption of marine omega-3 is safe, simple, cheap and effective.”
By ignoring these well-established, easy-to-change risk factors The Lancet Commission was able to reduce the claimed preventable risk to just 45 per cent, something that China’s leading prevention expert Professor Jin-Tai Yu of Fudan University in Shanghai strongly disputes.
“It may be possible to prevent up to 80 per cent of dementia cases if all known risk factors, including homocysteine lowering B vitamins and omega-3, found in oily fish, were targeted,” the APEG member said.
In response to a request for comment, The Lancet told GB News: "The 2024 report from the Lancet Commission on dementia, prevention, intervention, and care includes a detailed summary of the latest evidence around diet and dietary interventions.
"The report builds on two previous Lancet Dementia Commission reports (2017 and 2020) to provide an up-to-date review of high-quality evidence across all aspects of dementia care and research and was published following rigorous external peer-review. Find out more about our editorial policies, here."
