Women’s Health Update

Two Botanicals for the Aging Brain

Tori Hudson, ND

Nootropics is a term used to describe those agents that improve cognition, memory, creativity, or motivation. Nootropic substances can be as common as everyday caffeine and nicotine, or stimulants such as amphetamine and methylphenidate, or many prescription items, including levodopa. Nootropic agents can also include plants, vitamins, or other dietary supplements. The following botanicals are two of the most significant current botanicals used for their nootropic effects.

Bacopa monnieri, is a well-known herb native to Australia and India. While it is commonly found as a weed in rice fields, it also grows throughout East Asia and even the United States. It has a long historical use in Ayurvedic medicine in areas of memory and intelligence. The entire plant can be used as medicine. The main nootropic constituents of bacopa are believed to be of triterpenoid saponins known as bacosides, with jujubogenin or pseudo-jujubogenin moieties as aglycone units.¹ There are 12 bacopasides analogs called bacopasides I–XII that have been identified.^{2, 3, 4} There are several alkaloids, including brahmine, nicotine, and herpestine as well as  d-mannitol, apigenin, hersaponin, monnierasides I–III, cucurbitacins and plantainoside B. The most studied constituent, extracted from the whole plant, has been bacoside A.

While many of the pharmaceutical nootropics are potentially addictive (eg, caffeine, nicotine and psychostimulants), bacopa appears to nourish rather than deplete neurons. Historically, bacopa was used by Vedic scholars to help them memorize lengthy hymns and scriptures and many ancient texts refer to the herb’s ability to sharpen intellect and improve mental deficits. It is often found in many Ayurvedic preparations for cognitive dysfunction.

There is conflicting evidence as to the effects of bacopa on cognitive function, but possible mechanisms for cognitive improvement include modulation of acetylcholine release, choline acetylase activity, and muscarinic cholinergic receptor binding. In the laboratory, bacopa inhibits acetylcholinesterase activity and may also have neuroprotective effects, including the ability to protect neurons from beta-amyloid-induced cell death.

At least six high-quality randomized, double-blind, placebo-controlled human trials have been conducted. Pase et al. conducted a systematic review, finding some evidence that bacopa could be used as a memory enhancer even in individuals without dementia.⁵ These same six studies met the final inclusion criteria and were included in the systematic review. All the trials were conducted over 12 weeks. Not all the trials used the same dosage and three different bacopa extracts were used at dosages of 300-450 mg extract per day. All the reviewed trials evaluated the effects of bacopa on memory, and other cognitive function tests were less well studied. Across all the studies, bacopa improved performance on 9 of 17 tests in memory free recall. There was no real evidence of any other cognitive domain enhancement.

In a meta-analysis, Neale et al. compared the nootropic effects of Bacopa monnier to Panax ginseng and modafinil (an eugeroic-wakefulness drug).⁶ Chronic bacopa use produced the most consistent and largest effect sizes of the three. Bacopa showed small- to medium-effect sizes for attention and information processing tasks. Larger-effect sizes were evident for auditory verbal learning tasks, including delayed word pair memory, delayed word recall, and for protection from proactive interference during delayed memory. The highest effect sizes for cognitive outcomes were 0.77 for modafinil (visuospatial memory accuracy), 0.86 for ginseng (simple reaction time) and 0.95 for bacopa (delayed word recall). These findings support the use of bacopa, particularly in measures of verbal recall.

Highlighting a couple of the individual studies, Stough et al. conducted a randomized double blind placebo controlled trial in 46 healthy adults, examining the effects of bacopa on cognitive function in healthy individuals, using a bacopa supplement of 300 mg/day standardized to 55% bacosides for 12 weeks.⁷ A battery of eight tests was taken at five weeks and 12 weeks post administration, finding significantly improved speed of visual information processing, learning rate, memory consolidation, and state anxiety compared to placebo, with maximal effects evident after 12 weeks.

A study conducted in Portland, Oregon, evaluated the effects of Bacopa monnieri whole plant standardized dry extract on cognitive function in healthy elderly participants.⁸ This randomized, double-blind, placebo-controlled clinical trial had a treatment period of 12 weeks. Fifty-four men 65 or older (mean of 73.5 years) without dementia were enrolled and randomized to bacopa or placebo. Forty-eight (48) completed the study with 24 in each group. Participants were given Standardized B. monnieri extract 300 mg/day a similar placebo tablet orally for 12 weeks.

Bacopa participants had enhanced Rey Auditory Verbal Learning Test (AVLT) delayed word recall memory scores relative to placebo. Other cognitive measures such as the Stroop task results were similarly significant, with the bacopa group improving and the placebo group unchanged. Depression and anxiety scores and heart rate decreased over time for the bacopa group but increased for the placebo group. No effects were found on the Divided Attention Task (DAT), and the Wechsler Adult Intelligence Scale (WAIS) letter-digit test of immediate working memory. Overall, the study provided further evidence that bacopa could enhance cognitive performance in aging individuals.

Bacopa has also been studied in children for effects on cognition and learning. A systematic overview published in 2017 gives a good insight into the research and potential.⁹ Nine trials met the inclusion criteria and five studies reported sufficient data for effect size analysis. Most of the improvements reported were in behavioral outcomes. Cognitive abilities and behavioral outcomes were reviewed in six studies, with visual perception, impulsivity, and attention demonstrating the greatest improvements.

Dosages, Side Effects, Toxicity, Contraindications

Bacopa has been used safely in children and adults in studies up to six months in duration. Common dosages range from 350-640 mg/day; the part used is the leaf.

Drug interactions that are moderate and thus caution should be considered include the following:

• Acetylcholinasterase inhibitors

• Anticholinergics

• Cholinergics

• Cytochrome p450 1A2 substrates

• Cytochrome p450 2C19 substrates

• Cytochrome p450 2C9 substrates

• Cytochrome p450 3A4 substrates

Minor drug interactions include thyroid hormones.

Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels and have cholinergic effects, and thus should be used with caution in those individuals with bradycardia, gastrointestinal or urogenital obstruction, peptic ulcer disease, asthma and chronic obstructive pulmonary disease. Thyroid might also increase thyroxine levels (T4).

Bacopa is generally well tolerated, but there are reports of increased stool frequency, nausea, and abdominal cramps. Less common side effects could include dry mouth, muscle fatigue, flatulence, bloating, decreased appetite, headache, palpitations, drowsiness, sleep issues, and vivid dreams.

Rhodiola rosea, or “golden root”, has been used for centuries in Eastern Europe, Scandinavia, and Asia. It has remained largely unknown in the West, until recently. Traditionally, Rhodiola rosea was used in folk medicine with a reputation to increase physical endurance, productivity, longevity, resistance to high altitude sickness, fatigue, depression, anemia, impotence, gastrointestinal ailments, infections and disorders of the nervous system.¹⁰

The root of Rhodiola rosea has six distinct groups of chemical compounds:

• Phenylpropanoids: rosavin, rosin, rosarin

• Phenylethanol derivatives: salidroside (rhodioloside), tyrosol

• Flavonoids: rodiolin, rodionin, rodiosin, acetylrodalgin, tricin

• Monoterpenes: rosiridol, rosaridin

• Triterpenes: daucosterol, beta-sitosterol

• Phenolic acids: chlorogenic and hydroxycinnamic, gallic acids.

Rosavin is the constituent currently selected for standardization of extracts.¹¹

The properties of Rhodiola rosea to influence the cardiopulmonary system, central nervous system, and improve the ability to adapt to stressors have been attributed primarily to its influence on the levels and activity of serotonin, dopamine, and norepinephrine in different structures in the brain. It may be that the plant inhibits the breakdown of these chemicals and facilitates the neurotransmitter transport within the brain.¹² In addition to these effects on the central nervous system, rhodiola has been reported to increase the chemicals that provide energy to the muscle of the heart and to prevent the depletion of adrenal catecholamines induced by acute stress.¹³

Historically, rhodiola was observed to act in humans as a tonic, increase attention span, memory and work performance. Two human studies were able to show that individuals with fatigue, irritability, insomnia and decline in work capacity responded favorably to a rhodiola dose of 50 mg, three times a day.^14,15

In another human study of 128 patients aged 17-55, rhodiola alleviated fatigue, irritability, distractibility, headache and weakness in 64 percent of the cases. In a study of students, physicians and scientists, rhodiola was given for two to three weeks beginning several days before intense intellectual work such as final exams. The extract improved the amount and quality of work and prevented decreased performance due to fatigue. Using rhodiola during final exams appears to be beneficial as well. Medical students took a rhodiola extract for 20 days and had significant improvements in mental fatigue, general well-being, final exam grades and physical fitness.¹⁶

Case studies have reported that Rhodioa rosea can help with depressive syndromes, memory loss, anxiety, cognitive dysfunction, and menopause related symptoms.

Practitioner Dosing, Side Effects, Toxicity and Contraindications

Rhodiola rosea has a very low level of toxicity in animal studies. The toxic dose is calculated in humans to be about 235 gm or 235,000 mg for a 70 kg man. The typical daily dose for chronic administration is 360-600 mg per day when standardized for 1% rosavin, 180-300 mg when standardized for 2% rosavin, or 100-170 mg when standardized for 2.6% rosavin. There are also products available that list the rosavins in milligrams; examples include 6 mg of rosavins per 120 mg of rhodiola root or 12 mg of rosavins per 240 mg of rhodiola root. These formulations are an even more robust 5% rosavin content; yet still, all of these provide a large margin of safety. Overall, there are very few side effects with rhodiola. Some anxious individuals may be over activated and become agitated. Rhodiola rosea may also interfere with sleep in some individuals and should be taken early in the day. It should be avoided in individuals with bipolar disorder who have a history of manic episodes when given antidepressants or stimulants and should be used with caution in general, in those with bipolar 3disorder. If use is desired just prior to an academic exam or an athletic competition, the suggested dose is three times the dose for daily consumption for one dose. Safety issues are not available for pregnancy and lactation, so rhodiola should therefore be avoided.