What the Research Shows About the Brain After 40

Four ingredients, the changes they address, and an honest account of the evidence behind their benefits  

If you’re past 40, then you may have noticed that your brain feels a bit different to the way it did at 35. It might be a little slower to retrieve the right word. You might find it harder to sustain concentration through a long afternoon. Perhaps you tire quicker when the cognitive demand is high. You're not imagining it, and you're not alone in struggling to explain it.  

The changes are real and have specific biological causes. The good news is that several of them can be addressed through nutrition in ways that are supported by the research. The strength and nature of that support varies by ingredient. This article shines a light on those distinctions and will hopefully make things a lot clearer.  

We are looking at four ingredients which are included in the get dopa formulation, which are especially important to how the brain changes as life's demands on it evolve. These are: Phosphatidylserine, Ginkgo Biloba, Bacopa Monnieri, and vitamin B12.
   

Why the brain changes and why it's not just 'ageing'  

The term 'ageing' is often used as a catch-all for a wide range of cognitive changes that deserve more specific explanations. Understanding these explanations is more useful than a generic catch-all term, because understanding particular causes can point towards specific support. 

Four things happen gradually over our lifetimes, and these can be related to the cognitive experience many people describe as affecting them in their forties:  

• The composition of cell membranes shift. Cell membranes are the semi-permeable barriers that keep the right contents within each cell, and allow some microscopic elements to move into the cell and others to move out. These membranes are made up largely of lipids, a type of fat compound, which arrange themselves into set patterns within the membranes. They are important in all cells, but in brain cells or neurons, changes can affect how efficiently signals pass between cells. This is one of the mechanisms behind slower recall and processing speed. This is not reduced intelligence, but a reduction in signalling efficiency.  
  
• B12 absorption can decline in efficiency. The stomach protein required to absorb B12 from food can become less effective over time, meaning B12 levels can become sub-optimal even with a dietary intake that was previously adequate. Sub-optimal B12 is associated with slower thinking and difficulty concentrating.
  
• The brain's reserve capacity decreases. The brain is surprisingly good at working around gaps and inefficiencies. Up to a point. As the cumulative demands of adult life build, its reserve capacity is drawn on more heavily. What used to feel effortless starts requiring more cognitive resource and more conscious effort.
  
• Circulation efficiency can shift. The brain has no reserves of oxygen or glucose – it therefore depends entirely on consistent blood supply to function. As cardiovascular efficiency changes gradually over a lifetime, the steadiness of that supply can change with it. This is one reason why ingredients studied for their relationship with circulation are especially relevant to the cognitive experience of getting older. 
  
  

Phosphatidylserine: the membrane ingredient  

Phosphatidylserine (PS) is a phospholipid. This is a type of fat that forms a critical component of brain cell membranes. The brain is particularly rich in PS because the signalling demands on brain cells are exceptionally high, just think of all those billions of brain cells firing signals to each other. What PS does at the membrane level is support the fluidity that allows signals to pass through and between cells efficiently.  

As PS levels in brain cell membranes change naturally over a lifetime, signalling efficiency can change with them. This is one of the specific mechanisms behind the slower recall and processing speed many people notice. Not a loss of capability, but a change in the speed and ease with which the brain accesses what it knows.  

PS has one of the most substantial evidence bases of any ingredient in cognitive nutrition. Multiple clinical trials have examined its effects in adults, with consistent findings across memory and cognitive performance measures. In the United States, PS carries an FDA-qualified health claim, a designation granted only when a body of clinical evidence supports a potential relationship between an ingredient and a health outcome. It is saying that the evidence is promising but not yet conclusive. FDA approved would require a higher level of evidentiary proof. These are US-specific designations and do not apply under UK regulation. But it is an indicator of the depth and quality of the research.  

Some products include PS at doses too small to be relevant to the evidence. get dopa includes it at 100mg, which is the dose consistent with the research. The dose matters as much as the ingredient. 
  

Ginkgo Biloba: circulation and the brain's fuel supply  

Ginkgo Biloba is a botanical ingredient. It is one of the most highly researched botanical ingredients in the world, having been studied extensively in the context of memory, concentration, and cognitive function. The consistency of that research across decades and populations is why it appears in a formula built around evidence.  

The primary mechanism studied is Ginkgo's relationship with blood circulation. The brain requires a good and consistent supply of oxygen and glucose to function. Both are carried to the different parts of the body by the blood circulation system. The brain is in fact the most energy-intensive organ in the body, yet it has almost no reserves of either oxygen or glucose to fall back on. Most of this research has examined the extent to which Ginkgo supports the circulation that delivers this steady supply, and to what extent this is linked to cognitive outcomes.  

Systematic reviews and meta-analyses of broader research data have explored these questions, and findings suggest Ginkgo at standardised doses may support aspects of memory, concentration, and circulation relevant to brain performance, particularly in the context of the gradual changes associated with getting older. By standardised doses we mean doses where the active compound content is known, consistent, and comparable to what was used in the research. 

Bacopa Monnieri: working memory and the patience it requires  

Bacopa Monnieri is another botanical extract. It has been used in the Ayurvedic tradition for centuries and importantly has more recently been the subject of a growing body of modern clinical research. Randomised controlled trials have examined its effects in healthy adults, and consistent findings include improvements in working memory, recall speed and the ability to sustain cognitive performance under demanding conditions.  

This is directly pertinent to what many people in their forties describe. Not a decline in raw intelligence, but a reduction in the ease and speed of memory retrieval, and a sense that sustained concentration now requires more active effort than it used to. These are precisely the cognitive areas that Bacopa has been studied in. 

Bacopa is also a botanical ingredient with health claims that are on hold under EU/UK regulation. A lot of research has been done and the results are meaningful. A systematic review of published trials found consistent patterns across several cognitive domains, but once again, the formal authorisation process is not complete in the UK/EU. We have therefore described the research as just that; research. 

One of the important distinguishing features of Bacopa is its timeline. The beneficial effects observed in the published trials consistently emerge after eight to twelve weeks of daily dietary supplementation. It is not a pharmaceutical drug. It does not have an observable effect after a single dose, and not within hours. The reason for this is that Bacopa works through mechanisms that take time to establish rather than producing an acute pharmacological effect. get dopa therefore sets a twelve-week expectation, and the Bacopa is included at a full research-consistent dose: 100mg from a standardised 11:1 extract, equivalent to 1,100mg of the raw herb. 

IN SUMMARY  

→ Phosphatidylserine (100mg)  

Phospholipid which forms part of brain cell membrane structure. It supports signalling efficiency between brain cells. Well-researched. Included at a research-consistent dose. PS has a strong research base, but today is still without formal UK/EU authorisation. 

→ Ginkgo Biloba (36mg using 50:1 standardised extract, equivalent to 1,800mg of raw herb) 

A botanical studied for its effect on memory, concentration, and circulation relevant to brain function. EU health claim on hold pending EFSA evaluation. Use of standardised extract ensures meaningful active compound content.  

→ Bacopa Monnieri (100mg using 11:1 standardised extract, equivalent to 1,100mg of raw herb) 

Botanical that has been researched for its effect on working memory, recall speed, and sustained cognitive performance. EU health claims are on hold pending EFSA evaluation. Effects build over a 8–12 week period. Included in the get dopa formula at the research-consistent dose.  

→ B12 as methylcobalamin (50μg) 

Authorised UK health claim. It contributes to normal psychological function and the normal functioning of the nervous system. Because the active form is included in the get dopa supplement, no conversion inside the body is required. The dose assists with the variability in absorption capability that can come with age.  

B12: the authorised claim. Why absorption changes matter  

Vitamin B12 is the ingredient in this group that has the clearest regulatory position. It contributes to normal psychological function and to the normal functioning of our nervous systems. Both these statements are formally authorised health claims under UK/EU regulation and both are directly relevant to the cognitive experience that this article is about.  

What requires more of an in-depth explanation is why B12 becomes increasingly important as we get older, and why the form in which it’s consumed matters so much. 

Our ability to absorb vitamin B12 depends on the presence of a protein called ‘intrinsic factor’. This is a protein that is produced in our stomachs. ‘Intrinsic factor’ production by the body can decline over time and this in turn reduces the efficiency of B12 absorption from our food, even when dietary intake might appear to be adequate. This means our B12 levels can gradually drift down to sub-optimal amounts which, whilst not clinically deficient, are below the levels at which the brain functions optimally. This drift can be slow. It is often asymptomatic. Frequently it goes undetected. 

There are cognitive experiences of sub-optimal B12 levels that include slower thinking, difficulty concentrating, and a sense of mental heaviness that feels disproportionate to the task. These experiences can overlap with what many people attribute simply to getting older. Sometimes this attribution might be accurate, sometimes it's a B12 story which can be helped. 

To provide that help, get dopa uses methylcobalamin. This is the active form of B12 that requires no conversion by the human body. The dose used is 50μg and 2,000% of the reference intake. It's a deliberately big dose that reflects both the bioavailability advantage of using the active form and the higher absorption demands that can come with age. The body will take in as much as is needed and, as it's a water-soluble vitamin, any left over is simply excreted. 

The honest summary of the evidence  

The four ingredients we have covered in this article are each backed by genuine research. But due to their nature, they sit in different regulatory categories. The honest account of each one looks different as a result.  

B12 is well accepted and has an authorised claim. PS has a strong research base, but today is still without formal UK/EU authorisation. Ginkgo and Bacopa both have substantive research on them but have on-hold botanical claims. These distinctions might not change the quality of the underlying science, but they do reflect the time taken to prove clinical results and therefore how confidently a supplement supplier can be in stating the outcomes on its labels and promotional materials. Some suppliers might prefer not to make that distinction visible. We do the opposite. We are as clear and honest as we can be, so that you can make informed choices.  

We believe that transparency about what is known, what has been researched, and what is still pending regulatory confirmation is a more useful thing to put in front you. In other words we reject uniformly confident label claims which have been crafted to obscure rather than illuminate. If you're in your forties or maybe beyond, then you can handle the nuance. 

KEY TAKEAWAYS  

• Our cognitive experience is affected by several specific biological changes as we get older. These can include changes in the membrane composition of our brain cells, declining B12 absorption efficiency, and reduced cognitive reserve capacity. These are specific things which often get submerged under the simple catch-all description of 'ageing'.
• Phosphatidylserine provides support for brain cell membrane structure and therefore signalling efficiency. There is a strong research base for it and it's included at 100mg. Claims for it are not formally authorised under UK/EU regulation in the way a vitamin like B12 is.
• Ginkgo Biloba has been the subject of extensive study, particularly with regard to memory, concentration, and the link between circulation and brain function. Its regulatory health claims are on hold. The get dopa formulation uses a 50:1 standardised extract which is equivalent to 1,800mg of the raw herb. Standardisation of dose is important here. 
• Bacopa Monnieri. Multiple clinical trials focused on working memory and sustained cognitive performance have been completed and the results published. Its regulatory health claims are on hold. A feature of Bacopa is that the effects build steadily over a period of 4–8 weeks.
• B12 is a widely researched vitamin that is equally widely accepted. It carries authorised UK health claims for normal psychological function and normal nervous system function. Other studies have examined the extent to which absorption efficiency can decline with age. The get dopa formulation uses methylcobalamin, which is the active form, at 50μg (2,000% RI).
• An honest formula is underpinned by full transparency about the regulatory status of different ingredients, and the difference between authorised claims, strong research and on-hold botanical official approvals. 

NEXT IN THE SERIES

Part five of our six part series looks at the gut-brain connection. Specifically: why there are more nerve cells in your gut than in your spinal cord, what the vagus nerve has to do with how you think and feel, and why Lactobacillus rhamnosus is in a cognitive formula at all.

You may have questions about this article or the get dopa formula. If so, you can reach us at hello@getdopa.com