Within this past year I had the opportunity to reformulate a brain product. It had a few ingredients with good, published science behind them, but there was an issue with efficacy. For any formulator, the first goal is to use ingredients that have published research to make a claim. So you must align the ingredients – and dosage levels – that are used to support the marketing message, and then look at your costs.
The friction between science and marketing goes on every day, but when dealing with the fragile brain it is perhaps more important than ever to remember safety. The brain controls all body functions including memory, hunger, thirst, movement and sleep. It is quite intricate, with many different neurotransmitters, all of which are continuously working.
Consumers, of course, are stressed out with intense high levels of anxiety and lows that lead them into depression. A few causes could be related to adrenal gland dysfunction or hypoglycemia (low blood sugar). In many years of health coaching, I have seen problems corrected by simply changing the diet. Possible or not, consumers seek the magic bullet to bring about a positive mood and to walk in peace day and night with sustained energy levels without crashing.
One concern I have is that some formulators have a “kitchen sink” mentality and build brain formulas for healthy consumers that include many different ingredients with the same mechanism of action, or they may throw in extra ingredients just to make the formulation unique. For instance, a formula may include various compounds at effective levels that inhibit acetylcholinesterase.
Acetylcholinesterase inhibitors inhibit the enzyme, cholinesterase, which both increase acetylcholine levels as well their duration in order to improve cognitive function. This could be dangerous because of the overstimulation of acetylcholine. At this time, there is not enough known about of the consequences. Acetylcholine is a brain neurotransmitter involved in learning, memory and cognitive function. It plays a role in sending messages from motor nerves to muscles and has been shown to be deficient in those with Alzheimer’s disease. These formulas may pose a risk for healthy people who take them long term.
In addition, there has been concern with acetylcholinesterase inhibitors taken in combination with FDA-approved Alzheimer's drugs, which could cause an increased risk of serious side effects. For this reason, products should include a warning for people taking these products who are already taking drugs that affect acetylcholine.
Some of the dietary supplement ingredients that influence acetylcholine levels are acetyl L-carnitine, phosphatidylserine, vinpocetine, dimethyl amino ethanol (DMAE), Huperzine A, lecithin, citicholine such as in Kyowa Hakko's Cognizin and a few of the B vitamins such as pantothenic acid and thiamin. There are several categories of brain products, but I will address three distinct areas of brain function, even though they may share one common thread of acetylcholinesterase inhibitors.
Cognitive performance product formulation
Traditional things people look for are improved memory, alertness and focus. Consumers may select this type of product if they experience brain fog, which is a condition that affects many people. It is distinguished by a reduction in clear thinking, confusion and loss of memory. Many times this can be related to hypoglycemia or other health conditions.
Various compounds that support cognitive performance, but may also fit into the other categories as well include:
Acetyl-L-Carnitine (ALC) is the acetylated ester of the amino acid L-carnitine. ALC is found naturally in human brains and it helps to increase acetylcholine levels, thereby improving mental function. It is believed it mimics acetylcholine in its actions. Doses of approximately 1,500-2,000mg/day have been shown in research to prevent the brain from aging.
DMAE (Dimethylaminoethanol) is a chemical compound that has been studied since the 1950s using the branded name Deanol. DMAE is found naturally occurring in foods like anchovies and sardines, but levels are low compared to doses added to formulations. DMAE has the ability to improve learning, cognitive function and memory by increasing acetylcholine levels.
Fisetin is a flavonoid found in fruits and vegetables. The branded product Cognisetin is sold by Cyvex Nutrition and has been shown to improve memory when provided at doses of 50-150mg/day.
Omega-3s from different sources has been shown to improve cognitive function. Low DHA levels in the body have been correlated with poor cognitive performance. Although both EPA and DHA are important in proper balance, DHA stand-alone products have science to demonstrate their benefit in improving mental function and memory, such as EPAX 1050 TG.
On the food side, there are companies such as Novus International that provide enhanced nutrition to whole eggs. For example, they have the ability to feed chickens a high omega-3 diet, which provides eggs with DHA omega-3 at a standardized level so that marketing can make structure/function claims revolving around the benefits of omega-3s including brain health claims. This helps companies to build brand trust.
Huperzine A is a compound from China that is derived from the club moss Huperzia serrata. It has been shown to inhibit acetylcholinesterase, with various Chinese studies showing it improves cognitive function and memory. Georgetown University has been investigating Huperzine A for more than 12 years for its benefits in improving cognitive function and memory.
Vinpocetine is derived from vincamine, which is found in the periwinkle plant. It possesses vasodilator properties and has been used to improve cerebrovascular circulation. Studies also show that it also has a positive, direct effect on nervous tissue cells. Many clinical studies have been performed with it, including a human trial where vinpocetine was included in various coffee, tea or cola beverages. The study showed that it improved cognitive capacity and memory. The study was performed by the European chemical and pharmaceutical company, Covex, which is said to supply about 80 percent of the market, and is presently sold under the brand name Intelectol.
Bacopa monniera is an interesting Ayurvedic botanical from India with extensive history of use. It is used to promote memory and cognitive function. It is definitely one to investigate further for formulating.
Vitamin B1 (Thiamin) is used in the metabolism of glucose for the manufacturing of energy. It is involved in the release of acetylcholine, thereby affecting focus, perception and memory.
Yamabushitake (Hericium erinaceus) is a botanical that has demonstrated in Japanese research to significantly improve cognitive function. Draco Natural Products is a raw goods material supplier that carries this ingredient.
Mood product formulation
This category includes up and down feelings that consumers may experience including mild depression, hormone imbalance and anger.
St. John's wort (Hypericum perforatum) is one of the most popular botanicals to help improve the mood. It has been used in many clinical studies showing that it helps to alleviate mild to moderate depression. Many consumers fear prescription pharmaceuticals and will select a product such as St. Johns wort because it is a dietary supplement.One difficulty in marketing products such as St. Johns wort is that customers expect a mood change immediately, but according to the research it may take as long as 4 to 6 weeks. A formulator may consider adding language to the product directions that encourages use for a particular length of time. Of course an attorney specializing in FDA/FTC issues should review any such language prior to marketing.
St. John’s wort contains the actives, hypericin and hyperforin, but there is controversy as to which is the key component. The recommended dosage for St. John’s wort is 900mg/day, standardized to 0.3% hypericin. It is wise to review and investigate hyperforin research. The daily dose of 45mg hyperforin is what is recommended.
Rhodiola rosea is a so-called adaptogenic botanical used traditionally for improving moods and reducing fatigue and nervous tension. Also, it is used in sports products to increase physical endurance. Research performed on students showed that rhodiola was reported to lower mental fatigue and improve a feeling of well being. It is one of the ingredients that you may not feel right away, but the science shows that long-term intake demonstrates results.
DL-phenylalanine (DLPA) is a combination of two amino acid isomers, L-phenylalanine and D-phenylalanine. Research shows that DLPA reduced depression in a significant number of people with doses as low as 150-200mg/day. The research may not be strong enough to make a claim, but it is a compound to consider.
Stress product formulation
This category includes anxiety, which can arise from life events such as divorce, loss of a loved one, insufficient sleep, or physical stress from sickness and/or pain.
L-theanine is an amino acid found naturally in green tea. The patented form, branded as Suntheanine from supplier Taiyo International, is not from green tea, but is manufactured through a fermentation process. It has many clinical studies demonstrating that it stimulates alpha waves in the brain, which are associated with relaxation. The effective dose is 50-200mg/day.
Passionflower (Passiflora incarnata) is used throughout Europe to address nervous tension. Some research shows that it helps to improve mood. It has been shown in one study to improve anxiety equally to a prescription drug. It is believed that its flavonoids provide a sedative effect in the central nervous system.
Kava (Piper methysticum) is a well-known herb used to reduce anxiety, insomnia and restlessness without drowsiness. There have been approximately 10 clinical trials using kava at around 400mg/day, as a standardized extract, with most of them showing a significant reduction in anxiety. There was a scare a number of years ago of kava causing liver damage, which caused many formulators to hold back its use in products. It is wise to always check the regulatory and safety issues on ingredients prior to adding them into formulas.
Based on suggestions made by the American Botanical Council (ABC) to the consumer, formulators who use kava in formulations should provide a warning on the label. ABC recommended that it should not be used by anyone who consumes alcohol regularly, nor by those with liver problems, nor by anyone who takes prescription drugs that have adverse effects to the liver. ABC suggests that kava should not be taken daily for more than four weeks and that consumers should consult their physician if they have a history of liver problems or if they suspect they have a liver condition before taking it.
Hops is an extract and used for flavoring and preserving beer. It grows wild in Asia, North America, Europe and Australia. Research has shown that it helps to reduce anxiety and provides a calming effect, but most of the research has been in animals so more evaluation is needed in humans to determine its benefits and correct dosage.
Magnesium is an important mineral used by the body in numerous chemical reactions. It has been reviewed and believed to be associated with some anxiety disorders. It has been used in older human trials showing it was beneficial especially when used with vitamin B6 or in a multiple vitamin, although one would not usually feel any immediate benefits. Further research needs to be performed.
There are many ingredients for cognitive function, improved mood, and to handle stress. The objective is to thoroughly review all the research on these ingredients and make wise choices in formulating. Remember – more is not necessarily better. These products have the potential for great success when the formulator uses wisdom, reviews the scientific literature carefully on ingredients and makes wise choices in formulating.
Judi Quilici-Timmcke, Ph.D., is a scientist/technical consultant and product formulator for companies in the dietary supplements industry. She has secured for companies exclusive and patented ingredients, has testified in court as an expert, and also is a health coach.
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