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Uncluttering the brain health ingredient landscape

Mental health and cognition continue to be hot topics, creating formulation opportunities for researched ingredients like SAMe, folate and glutathione.

Beatrice Minin

December 9, 2022

7 Min Read
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Having experienced the effects of lockdowns and the pandemic, the global public has reprioritized its health focus: It’s now placing the spotlight on mental health like never before, with a recent IPSOS study ranking it just after Covid-19 and cancer as the biggest health concerns.

But overall brain health consists of more than just mental health; it also means cognitive health—or the ability to think, learn and remember. Prioritizing both mental and cognitive health means prioritizing overall quality of life at all ages.

This increased focus on overall brain health is also reflected in the market, where the global brain health supplement market accounted for $8 billion in 2021, with a promising compound annual growth rate (CAGR) of 9% expected from 2021-2028. This puts the market at $15 billion in 2028, opening many opportunities for products delivering brain health benefits.

More people = More cognitive decline

Across the globe, people are living longer: in 2019, around 700 million people worldwide were age 65 or older, with this number anticipated to increase to more than 1.5 billion in 2050.

At the same time, Alzheimer's and dementia incidences are rising. According to the World Health Organization (WHO), 139 million people are expected to be dealing with dementia in 2050, up from 55 million people in 2021.

Consumers are starting to notice the detrimental effects of cognitive decline in their elders, and as a result, consumers are shifting from embracing a holistic and preventive approach to aging gracefully. They’re committing to preserving their mental sharpness and mitigating age-related cognitive decline, from mild impairment to neurodegenerative diseases.

In this context, the demand for cognitive support supplementation is growing steadily, opening exciting new ingredient opportunities for dietary supplement and functional food brands.

Multifaceted brain, cognitive health ingredient

When it comes to cognitive dietary supplement formulation, many ingredient options work with the body to support mental health and well-being. The increased focus on brain health supplements means more products entering the market, which can create a struggle for brands to stand out.

Selecting unique, clinically supported ingredients is one method for brain health brands to differentiate. S-adenosyl-L-methionine (more lovingly referred to by the brain health market as SAMe) is one of those.

SAMe is one of the most crucial methylating agents in the human body, essential to sustain various functions, including detoxification, regulating genes, mood balancing and controlling inflammation.1,2 SAMe operates as a methyl-donating cofactor, synthesized as part of a sequential reaction pathway (known as one-carbon metabolism or methylation cycle) involving folate and vitamin B12.

Thanks to its methyl donor activity, SAMe plays a multifaceted role in brain health:

• Neurotransmission: Through a multistep pathway involving methyl donation, SAMe is involved in the synthesis of neurotransmitters dopamine, serotonin and norepinephrine.3 This helps to normalize mood, moderate behavior and promote well-being. Dysfunctions in the monoamine systems of neurotransmitters released in the brain are involved in developing depression and other mood disorders. Exogenous supplementation of SAMe may result in increased synthesis of these neurotransmitters, which may account for its mood-enhancer effects.

• Neuroplasticity: SAMe is involved in forming myelin that surrounds and protects neuron axons.4 It can improve brain-cell membrane fluidity, enhancing the function of neuroreceptors.

• Neuroprotection: SAMe helps produce one of the body's most powerful antioxidants, glutathione, also known as the master antioxidant.5 Glutathione can efficiently scavenge various free radicals that could lead to oxidative stress, resulting in brain damage.

Since SAMe and methylation levels decrease with age,6 this can slow down the vital activities that SAMe sustains. For this reason, SAMe supplementation may contribute to supporting mood, brain function and neuronal health, and may counteract the onset of cognitive health-related problems, according to a scientific textbook on nutraceuticals.

In supporting mood and promoting mental well-being, SAMe can be used alone or with other antidepressants.7

Just as mental and cognitive health work together to improve overall brain health, two other key actors are involved in the methylation cycle and play a fundamental role in cognitive health: folate and glutathione.

Folate, or 5-MTHF, is the biologically active form of folic acid that the human body can immediately utilize (even if affected by enzyme polymorphism) without needing any metabolization.8 In the methylation cycle, along with B12, it supports the transformation of homocysteine to methionine, and then into SAMe.9

Folate is an essential nutrient that can enhance cognitive performance and help mild cognitive impairment by reducing homocysteine levels, a potentially crucial modifiable cause of cognitive dysfunction.10

As previously stated, glutathione is the body's master antioxidant that can help combat oxidative stress in the brain by scavenging free radicals. Maintaining adequate levels of glutathione is fundamental to preserving the brain health, improving its functions, and preserving brain health and its functions, including memory.11

Chronic oxidative stress, pathogens and aging can reduce the body's presence of glutathione, so restoring it through supplementation can contribute to optimal cognitive health.12

Taking control of cognitive health

If a person’s genes lay the groundwork for their overall mental and cognitive health, one’s environment undoubtedly shapes the final product. By embracing a more balanced sleep schedule, exercise and nutrition regiment, people can better influence their cognitive health. For consumers who struggle to take in the perfect balance of nutrients to help maintain this balance through the food they consume, dietary supplements focused on brain health can help fill gaps to support methylation, cognitive performance and mental well-being. For formulators thinking about their next brain health supplement, SAMe is the nutritional active that can take the stress out of the decision and help them compete in an increasingly competitive market.

Editor’s note: For more content on cognitive health, get ahold of our free digital magazine, “Brain games: Ingredients for mood, balance, performance.”

Beatrice Minin is market manager for the mood & cognitive health segment at Gnosis by Lesaffre. By exploring the potential of microorganisms and biotransformation processes occurring within our bodies, the company identifies molecules linked to cognitive health to develop nutritional solutions to support mood and brain health, such as Adonat Premium SAMe; Emothion, the crystalline form of S-Acetyl Glutathione; and Quatrefolic, the biologically active form of folate.


1 Gao J et al. “S-Adenosyl Methionine and Transmethylation Pathways in Neuropsychiatric Diseases Throughout Life.” Neurotherapeutics. 2018;15(1):156-175.

2 Bottiglieri T. “S-Adenosyl-L-methionine (SAMe): from the bench to the bedside—molecular basis of a pleiotrophic molecule.” Am J Clin Nutr. 2002;76(5):1151S-1157S.

3 Mischoulon D and Fava M. “Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence.” Am J Clin Nutr. 2002;76(5):1158S-1161S.

4 Lieber CS and Packer L. “S-Adenosylmethionine: molecular, biological, and clinical aspects--an introduction.” Am J Clin Nutr. 2002;76(5):1148S-1150S.

5 Cavallaro,RA et al. “S-adenosylmethionine prevents oxidative stress and modulates glutathione metabolism in TgCRND8 mice fed a B-vitamin deficient diet.” J Alzheimers Dis. 2010;20.4:997-1002.

6 Agrawal A et al. “Age-associated epigenetic modifications in human DNA increase its immunogenicity.” Aging (Albany NY). 2010;2(2):93-100.

7 Sharma A et al. “S-Adenosylmethionine (SAMe) for Neuropsychiatric Disorders: A Clinician-Oriented Review of Research.” J Clin Psychiatry. 2017;78(6):e656-e667.

8 Kelly CB et al. “The MTHFR C677T polymorphism is associated with depressive episodes in patients from Northern Ireland.” J Psychopharmacol. 2004;18(4):567-571.

9 Gilbody S et al. “Methylenetetrahydrofolate Reductase (MTHFR) Genetic Polymorphisms and Psychiatric Disorders: A HuGE Review.” Am J Epidemiol. 2007;165(1):1-13.

10 Ginsberg LD et al. “L-methylfolate Plus SSRI or SNRI from Treatment Initiation Compared to SSRI or SNRI Monotherapy in a Major Depressive Episode.” Innov Clin Neurosci. 2011;8(1):19-28.

11 Marí M et al. “Mitochondrial glutathione, a key survival antioxidant.” Antioxid Redox Signal. 2009;11(11):2685-2700.

12 Dwivedi D et al. “Glutathione in Brain: Overview of Its Conformations, Functions, Biochemical Characteristics, Quantitation and Potential Therapeutic Role in Brain Disorders.” Neurochem Res. 2020;45:1461-1480.

About the Author(s)

Beatrice Minin

Market Manager, Mood & Cognitive Health, Gnosis by Lesaffre

Beatrice Minin is market manager for the mood & cognitive health segment at Gnosis by Lesaffre. By exploring the potential of microorganisms and biotransformation processes occurring within our bodies, the company identifies molecules linked to cognitive health to develop nutritional solutions to support mood and brain health, such as Adonat Premium SAMe; Emothion, the crystalline form of S-Acetyl Glutathione; and Quatrefolic, the biologically active form of folate.

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