A vertically-integrated rebranding project to serve SAMe market quality expectation

Consumers are increasingly taking greater ownership of their health. They want to make choices because they are more aware of the role of nutrition in their health, they are well-informed and conscious of the health benefits of the ingredient/dietary supplement. At the same time, they are always conditioned by health, market, and media trends, that all strongly influence the final consumer choice.

The consumer’s perception of the quality of a dietary supplement is one of the main drivers of their purchases, even if often the consumer know nothing about developing the product, the science behind the product's claims, the potential issues involved (formulation, stability, packaging), and the efforts that company has made to ensure that the finished product delivered respects the declared and expected quality standards.

As a matter of fact, some ingredients are more sensitive than others, some should be carefully and specifically handled to maintain characteristics and stability, while others have an intrinsically stable profile and are more suitable to be combined with other ingredients and excipients. Clearly, the quality of the finished products depends on the quantitative content of the active ingredient (the assay determined by analysis) during all the shelf-life of the supplement.

This specific aspect is one of the most critical in S-adenosylmethionine (SAMe) dietary supplements: today its quantitative determination is a key requirement to define the quality of the dietary ingredient supplied and the finished products as well.

Adonat, the branded SAMe ingredient offered to nutritional supplements industry by Gnosis by Lesaffre, together with its sub-brands have undergone a vertically integrated rebranding project focused on the “SAMe PREMIUM quality” asset.

The project has the ambition to better service SAMe consumers, to meet rising demand to recognize the ingredient used in the supplement, often bought online, fitting the request of clear and trustable labelling.

Adonat, the leading SAMe brand of Gnosis by Lesaffre, offers the highest content of this biologically active ingredient, for a better beneficial health effect, and a reliable experience for both end manufacturers and final consumers. As the historical manufacturer of both nutraceutical and pharmaceutical-grade SAMe, Gnosis by Lesaffre applies its expertise and know-how to support the success of its customers and partners.

A “Branded House” strategy has been realized on the sub-brands to create a consistency of use, to build a common recognizable identity and a clearness in their use. The evolution consists in anchoring all sub-brands to Adonat PREMIUM SAMe as master brand, integrating a new baseline that can differentiate the offer and create a value for customers and final users.

SAMe and quality: the key aspect for efficacy

SAMe is an extraordinary dietary ingredient with proven effects on mood and cognition, liver and joint health, but it is naturally unstable, mainly sensitive to moisture and heat. Since its discovery, its own intrinsic instability has represented the main target of industrial development. Today the quantitative determination of the active SAMe is a key requirement to define the quality of the dietary ingredient supplied and the finished products as well.

In its native form it is an ionic chiral form – the (S,S) stereoisomer – extremely labile and rapidly degrading. Historically, it became industrially available in the nutraceutical market as an ingredient only after the stabilization of SAM-e ion as salt - like the disulfate p-toluenesulfonate - and as finished product in the form of enteric-coated tablets. Both processes (salt production and tablet manufacturing) are still protected by granted patents under Gnosis by Lesaffre know how. The enteric coating allows the dietary ingredient to be released in the intestine (duodenum), to optimize gastrointestinal tolerability and absorption, and in the meantime protects the dietary ingredient (contained in the tablet’s core) from degradation avoiding the contact with air humidity.

What is SAMe and how does it work in our body?

SAMe is a natural occurring physiological substance that is present in virtually all living cells. It is the most important methylating agent of the human body, and it is essential to sustain a variety of functions, including detoxification, energy production, immune function, maintaining and regulating genes, mood balancing and controlling inflammation. The biological function of SAMe has been extensively studied and characterized. Decreased or low SAMe levels in some biological fluids and tissues are often accompanied by severe physiological complications and have been associated with some altered body states, such as mood and cognitive impairment, liver disorders, but also joint discomfort.

The restoration of SAMe concentrations through its supplementation has been largely evaluated. Impressive literature extending back more than three decades supports its efficacy in brain support, mood, joint health and liver functionality as well.

SAMe and brain health

SAMe has a variety of biological effects in the Central Nervous System (CNS).

• Enhances cell membrane function and integrity
• Helps to restore cellular membrane fluidity
• Improves cellular communication between nerve cells
• Helps neurotransmitters delivering their messages to the receptor sites

SAMe is required for the synthesis of neurotransmitters such as norepinephrine, dopamine and serotonin. The lack of these molecules is involved in the development of mood disorders and depression.

Alterations in brain structures and functions are intimately tied to the alterations in cognitive functions. Age-associated neurological impairment can take a variety of forms including memory loss, senility, and dementia and may involve nerve cell deterioration.

The decreased methylation and the low availability of SAMe that occurs with age may induce several modifications and the mechanisms involved are still under extensive clinical investigation.

Certainly, it is known that the low level of SAMe impairs the production of adequate quantities of neurotransmitters. Moreover methylation by SAMe is a critical step in the production of an important phospholipid - the phosphatidylcholine - that is a component of neuronal myelin sheaths, and controls accessibility of cell membranes to outside signals, and thus affects how cells react to outside stimuli.

SAMe: Antiaging and longevity

SAMe is associated with longevity and aging, being implicated in all the major life-sustaining pathways and having a role in body stress responses, good stress management, inter- and intra-cellular communication, and mitochondrial functioning.

The mechanism of aging is characterized by many biologically significant changes in the morphology and physiology of different organs and tissues. The body is apparently less able to produce adequate SAMe levels with a decline of body’s ability to:

• properly operate methylation processes with alteration of DNA methylation
• produce adequate amount of antioxidants able to fight the free radical induced aging and inflammation
• promote the synthesis of compounds that are crucial to functions such as gene expression and DNA repair.

SAMe and liver

SAMe controls many vital hepatic functions as well as the response to liver injury. Its deficiency can impair many vital functions of the liver, which render it susceptible to injury by toxic agents, including alcohol.

Liver dysfunction is often associated with oxidative stress derived from an imbalance between the production and the removal of free radicals.

The alteration in the redox status of the liver may be induced by several factors but it is always characterized by an impaired and/or inadequate presence of SAMe that provides cysteine for the production of glutathione (GSH) - the major endogenous hepatoprotective agent.

SAMe and joint health

S-Adenosyl-methionine is an important factor in promoting the maintenance of healthy joints.

The mechanism of action may reside in the ability of SAMe to promote cellular proliferation and the regeneration of cartilage (increasing chondrocyte proteoglycan synthesis and proliferation rate), mediated through either methylation, trans-sulfuration and aminopropylation pathways.

Studies also support direct anti-inflammatory activity and tissue-healing properties that may help to protect the health of joints, and perhaps may lessen pain. The exact mechanism of SAMe in reducing pain is not known yet, but evidence suggests that the increased production of proteoglycans may play a role.

Gnosis by Lesaffre and Adonat

Since the beginning, Gnosis by Lesaffre has integrated the extensive knowledge of industrial manufacturing of SAMe with R&D activity, for optimizing quality and improving client service. Today Gnosis by Lesaffre intellectual property counts more than 10 patents on SAMe, ranging from manufacturing processes and stabilization of salts to the production of innovative forms of oral dosage.

^References

^{Bottiglieri T. S-Adenosyl-L-methionine (SAMe): from the bench to the bedside molecular basis of a pleiotrophic molecule. Am J Clin Nutr 2002}

 ^{Smazal A. Oral S-adenosyl methionine (SAM) mediates disruptions in methyl group metabolism due to retinoic acid therapy and alters neurotransmitter metabolism: implications for major depressive disorder. 2013}

^{Bottiglieri T et al. Cerebrospinal fluid S-adenosylmethionine in depression and dementia: effects of treatment with parenteral and oral S-adenosylmethionine. J Neurol Neurosurg Psychiatry 1990}

^{Sharma A et al. S-Adenosylmethionine (SAMe) for Neuropsychiatric Disorders: A Clinician-Oriented Review of Research. J Clin Psychiatry. 2017}

^{Noureddin M et al. Early treatment efficacy of S-adenosylmethionine in patients with intrahepatic cholestasis: A systematic review. World J Hepatol.2020}

^{Barve S et al. S-adenosylmethionine (SAM) deficiency in alcoholic/non-alcoholic steatohepatitis: potential therapeutic role of SAM. 2011}

^{Purohit V et al. Role of S-adenosylmethionine, folate, and betaine in the treatment of alcoholic liver disease: summary of a}

^{symposium. Am J Clin Nutr 2007}

^{Guo T et al. S-Adenosyl- L-Methionine for the Treatment of Chronic Liver Disease: A Systematic Review and Meta- Analysis. PLoS ONE 2015}

^{Blewett H, Joy H. Exploring the mechanisms behind S-adenosylmethionine (SAMe) in the treatment of osteoarthritis. Crit Rev Food Sci Nutr 2008}

^{Müller-Fassbender H. Double-blind clinical trial of S-adenosylmethionine versus ibuprofen in the treatment of osteoarthritis. Am J Med 1987}

^{Loenen WAM. S-adenosylmethionine: Simple Agent of Methylation and Secret to Aging and Metabolism’ In ‘Epigenetics of Aging’ 2009}