There are a handful of concerns that stand out as common reasons people consult a functional medicine or nutrition practitioner. With 40 percent of US adults living with obesity, weight loss is near the top of the list, keeping company with fatigue and chronic pain. Rounding out these issues that prompt people to seek help is brain fog. It’s easy to joke about how social media and smartphones are killing attention spans, but when sluggish thinking and lack of focus impact job performance or even personal safety, they’re no laughing matter. Caffeine or L-theanine from coffee or green tea can help can help, and medium-chain triglycerides and ketogenic therapies have garnered attention recently for their potential to support healthy cognitive function. Let’s take a look at a few lesser-known compounds that are research-proven to support healthy cognition and mental focus.

Bacopa monnieri

Bacopa has been employed for over 1400 years in Ayurvedic medicine, where it is recognized to “sharpen intellect and attenuate mental deficits.” Ayurvedic texts call Bacopa a medhya rasayana—an herb that sharpens the mind and intellect. The compound functions via multiple mechanisms, including antioxidant neuroprotection, inhibiting acetylcholinesterase, increasing cerebral blood flow, and modulating serotonin and dopamine. A meta-analysis of randomized controlled trials evaluating the cognitive effects of Bacopa determined that it has the potential to improve cognition, particularly speed of attention. The analysis included studies where Bacopa was given for a minimum of 12 weeks, and where there was no co-medication, which reduces confounding and helps confirm Bacopa as the active agent. A separate review of RCTs that also looked at studies of Bacopa supplementation administered for at least 12 weeks concluded that Bacopa improves memory (free recall), and may enhance other cognitive abilities.

Double-blind placebo controlled studies support the efficacy of Bacopa supplementation for improving working memory (especially spatial memory) in healthy adults. It may be effective even in acute doses: a study in which healthy adults were given a dose of a Bacopa extract or placebo prior to completing various cognitive tests, the Bacopa resulted in improvements in performance—within just 1-2 hours after dosing.

Bacopa may be especially helpful for children with ADHD. Six months of supplementation with a standardized Bacopa extract resulted in impressive symptom improvements in 31 children ages 6-12 diagnosed with ADHD. Restlessness was reduced in 93% of subjects and self-control improved in 89%. Symptom scores for learning problems, impulsivity, and psychiatric problems were reduced for 78%, 67%, and 52% of subjects, respectively. Looking at overall symptom reduction, 74% of the children exhibited up to a 20% reduction, with 26% showing between a 21% and a 50% reduction. Being that as much as 30% of children with ADHD don’t respond to common medications or eschew them due to adverse side-effects, Bacopa could be a useful adjunct to conventional therapy or used as part of a multifaceted approach.

Citicoline (Cytidine diphosphate choline, a.k.a. CDP-choline)

CDP-choline is an essential precursor for the synthesis of acetylcholine in the central nervous system as well as membrane phospholipids. (CDP-choline is the name of the endogenous molecule; the supplement form is called citicoline.) This molecule is produced endogenously from choline but the body has a high demand for it owing to the rapid turnover of cell membrane phospholipids. And considering most people in the US consume less than the recommended intake of choline (including 90-95 percent of pregnant women), supplementation with choline or related compounds may be beneficial for some individuals. Citicoline has very high oral bioavailability (over 90%). Its metabolites cross the blood-brain barrier and the compound is resynthesized in the brain after oral consumption.

A randomized controlled trial of citicoline in healthy adolescent males showed that compared to placebo, subjects taking citicoline showed improved attention, and improvements were greater with higher weight-adjusted doses. Citicoline supplementation was also shown to improve attention and task performance in a group quite different from adolescent males: women age 40-60. Numerous studies support the use of citicoline for cognitive impairment of any kind, but particularly that resulting from vascular origins. A trial of patients with first-time ischemic stroke “showed that citicoline prevented cognitive decline after stroke with significant improvement of temporal orientation, attention, and executive function.” The potential for this compound in promoting neuronal repair and neuroplasticity is exciting. It is already recognized as a potent nootropic that enhances focus, attention, and cognitive function in healthy individuals.

Epidemiological studies reveal a positive association between dietary choline intake or the blood free choline level and better cognitive performance in adults and the elderly, and vice-versa. A possible explanation for the beneficial effects of choline on cognition is, as mentioned earlier, that it’s a  precursor to phosphatidylcholine and acetylcholine. For those who don’t consume adequate choline-rich foods, “Supplementing the diet with citicoline ensures a steady

and adequate supply of CDP-choline to support growth, repair, and function of neuronal membranes and synapses in the brain.”

Huperzine A (HupA)

HupA is an alkaloid compound found in the Chinese herb Huperzia serrata. It naturally inhibits acetylcholinesterase, which underlies its potential efficacy in supporting cognition and memory. HupA has been shown to have greater oral bioavailability, more effectively penetrates the blood-brain barrier, and has longer lasting inhibitory effects on acetylcholinesterase compared to pharmaceutical cholinesterase inhibitors such as donepezil and tacrine. HupA has been studied for use in Alzheimer’s patients, and findings have been encouraging but improvements are generally small and further investigation is required. There may be a rationale for combining HupA with the green tea polyphenol EGCg for the purpose of supporting cognition. EGCg has been shown to boost HupA’s cholinesterase inhibiting activity, possibly by increasing binding affinity of HupA for serum albumin and consequently enhancing its transport. Researchers have speculated that this combination may allow for HupA to be equally effective at lower doses.

For individuals dealing with brain fog and problems focusing, numerous supplements are available that may be of benefit when added to a healthy diet, restful sleep, and appropriate physical activity.