Emerging science on dietary supplements and brain health

Анатолий Сав - Stock.adobe.com

According to the U.S. Census Bureau¹, the size of the U.S. population over the age of 65 is projected to reach 88.5 million by 2050, more than doubling the size of this population in 2010. As such, the size of the population of older adults with cognitive impairment and dementia is expected to grow to 13.8 million by 2050. Compare this to the approximate 5.5 million American with Alzheimer’s disease in 2017.² Considering the profound impact dementia can have not only on those suffering from it, but also their families in terms of emotional distress and financial burden, it’s important to find novel ways to reduce the risk or at the very least delay the onset of neurodegenerative diseases. A good place to start may be lifestyle.

“Worryingly, recent trends have shown that the onset of cognitive decline seems to be occurring earlier in our lifespans, with lifestyle choices found to be playing a decisive role,” said Professor Mohammed Gulrez Zariwala, B.Pharm, MSc, PhD, CMgr MCMI, FHEA, director of the Centre for Nutraceuticals at the University of Westminster. “Although it is not easy to quantify the precise extent, a good body of population-based studies have shown us that a diet rich in fish and vegetables, regular exercise and social interaction can dramatically slow the progression of cognitive decline. On the other hand, a diet rich in saturated fats and sugars, increased alcohol consumption and smoking can accelerate its progression.”

According to one study, older adults who adhered to four or five healthy behaviors simultaneously had a 60% lower risk of developing incident Alzheimer’s disease. These lifestyles include high quality diet, engagement in cognitive activities, regular physical activity, light to moderate alcohol intake, and not smoking.³ Zariwala cites a large population-based study from China that found people engaging in the healthiest lifestyle behaviors were significantly less likely to develop cognitive impairment compared to those with the least healthy behaviors.⁴

“A substantial body of evidence supports the benefits of lifestyle factors such as a healthy diet in maintaining cognitive health as we age. Diets such as Mediterranean-type diets rich in legumes and fish/seafood have shown a good association with the maintenance of cognitive health,” explains Zariwala. “Although the general trends reveal that such diets may go a long way in maintaining cognitive health, there may be dietary, cultural or socio-economic reasons that prevent many population groups from accessing such diets. This is where supplements can play a role in complementing nutritional interventions. As in the case of most effective supplement approaches, herbs and nutrients that show cognitive benefits can act as an adjunct to diet.”

The dietary supplement industry has long marketed products for cognitive health, claiming to support factors like memory with ingredients like gingko biloba based on their traditional usage. Confidence in supplements and their cognitive health claims varies, with most medical professionals not putting much stock in them largely due to the lack of large clinical trial data validating these benefits. Many take issue with what they view as deceptive and predatory marketing since people already experiencing cognitive deficits are unlikely to see any measurable improvements. That is not to say that certain nutrients and herbs cannot support cognitive health, simply that more substantiation is required.

“Unfortunately, quite a few herbs that have been claimed to have benefits have not been fully substantiated by a good body of scientific evidence,” says Zariwala. “There are others in use that have shown promise, but in my opinion, further research and in-depth investigations are required. Ashwagandha, saffron, brahmi (Bacopa monnieri), and rhodiola have all shown promise in this regard, but further work needs to be done to fully harness their benefits. As is the case with several botanicals, issues of purity, standardization, stability and bioavailability need to be addressed. Research by ourselves and others has seen potential with molecules such as curcumin, hydroxytyrosol, N-acetyl cysteine and palmitoylethanolamide (PEA) in the context of cognitive health, which needs to be explored further.”

According to Zariwala, potent antioxidant and anti-inflammatory ingredients such as curcumin and PEA show a great deal of promise in cognitive health because “the brain is highly susceptible to oxidative stress, and potent antioxidants…have a good scientific basis to be used to boost antioxidant defenses and counter the progression of cognitive impairments.”

For example, a recent study⁵ on which Zariwala is an author, found that co-administration of iron and curcumin significantly increase levels of brain-derived neurotrophic factor (BDNF). As Zariwala explains, while iron is a common nutritional deficiency that is corrected with iron supplementation, it is also a strong pro-oxidant, and excess iron can cause oxidative damage. A common side effect of iron supplementation is gastrointestinal discomfort, which Zariwala says happens when excess iron causes oxidative damage to the gut cells. Iron, Zariwala points out, is also an essential nutrient for cognitive development and function, with iron deficiencies being associated with fatigue, poor mood as well as poor concentration. Physiologically, iron plays an essential role in maintaining appropriate levels of BDNF, which is neurotrophic factor essential for neuronal health.

“Combining iron with curcumin showed an increase in BDNF levels in our study participants, even at low iron doses, and these levels were higher than those seen with iron alone,” explains Zariwala. “Our other results showed that the formulated curcumin we used in the study enhanced overall iron status. While we need to conduct further studies to clarify this, we proposed that the formulated curcumin may have helped optimize iron status to the level needed to amplify BDNF production. There is also the possibility that curcumin may also be acting in concert with iron at a molecular level in a synergistic manner to enhance BDNF synthesis. Again, this warrants further research.”

Another study Zariwala helped author found that PEA supplementation was associated with a significant increase in BDNF and improvements in memory.⁶ This small study of 39 participants also lays the groundwork for further research and substantiation, which is crucial not just to validate claims but also stimulate product innovation, Zariwala points out.

“Outcomes of high-quality clinical studies need to be followed up by more applied research to find ways to translate novel and exciting findings into viable products and equally support further basic and clinical studies to make the data more convincing and unequivocal,” he explains.

References

1. Vincent GK, Velkoff VA. The next four decades. The older population in the United States: 2010 to 2050. Current population reports. Washington (DC): US Census Bureau. 2010. p. 25–1138.
2. Alzheimer’s Association. 2017 Alzheimer’s disease facts and figures. http://www.alz.org/facts/overview.asp (accessed 2025-02-17)
3. Dhana, K.; Evans, D.A.; Rajan, K.B.; Bennett, D.A.; Morris, M.C.Healthy lifestyle and the risk of Alzheimer dementia. Neurology. 2020, 95(4), e374-e383. DOI:10.1212/WNL.0000000000009816
4. Jia, J.; Liu, Z.; Liang, Y.; Li, F.; Li, Y.; Liu, W.; Li, F.; et al. Association between healthy lifestyle and memory decline in older adults: 10 year, population based, prospective cohort study. BMJ. 2023. 380, e072691. DOI: 10.1136/bmj-2022-072691
5. Lorinczova, H.T.; Fitzsimmons, O.; Mursaleen, L.; Renshaw, D.; Begum, G.; Zariwala, M.G.Co-Administration of Iron and a Bioavailable Curcumin Supplement Increases Serum BDNF Levels in Healthy Adults. Antioxidants. 2020, 9(8), 645. DOI: 10.3390/antiox9080645
6. Kim, N.; Parolin, B.; Renshaw, D.; Deb, S.K.; Zariwala, M.G. Formulated palmitoylethanolamide supplementation improves parameters of cognitive function and BDNF levels in young, healthy adults: A randomised cross-over trial. Nutrients. 2024, 16 (4), 489. DOI: 10.3390/nu16040489