Specialty Compounds for Mood and Mental Wellness

Augmenting the options for companies looking to offer nutritional products for mood support are a number of specialty compounds. For example, the orthomolecule acetyl-L-carnitine (ALC) supports mitochondrial energy production and enhances the production neurotransmitter acetylcholine (ACh). Research shows ALC has the ability to enhance cognition and exert an antidepressant effect, particularly in elderly patients.^1,2 Italian researchers reported 1,000 mg/d of ALC could significantly improve depression parameters in fibromyalgia patients.³ ALC was also found in a trial out of Vita-Salute University San Raffaele, Milan, to exert similar antidepressant effects in dysthymic patients as the standard pharma treatment amisulpride.⁴ The research team suggested ALC may be a preferable treatment given the greater tolerability and chronic nature of dysthymia, which can require extended treatment.

ALC also works in concert with other specialty compounds to support mental well-being. One study out of the University of Massachusetts, Lowell, examined the impact of ALC plus S-adenosylmethionine (SAM-e) and the antioxidant N-acetyl-cysteine on neurotransmitter and cognitive function in animals.⁵ The combination enhanced cognitive function in mouse models of aging and neurodegeneration; behavioral abnormalities correlated with a decline in ALC, which suggests an important role in supporting neurotransmitter function.

SAM-e has been extensively studied for its antidepressant activity.⁶ It works as a methyl donor involved in the synthesis of several neurotransmitters, and studies have shown doses of 200 mg/d to 1,600 mg/d are superior to placebo and as effective as tricyclic antidepressants in alleviating depression.⁷ In fact, a pilot study in depressed patient with Parkinson’s disease who had not responded to pharma antidepressants found 10 weeks treatment with SAM-e (800 to 3,600 mg/d) produced at least a 50-percent improvement in depression symptoms.⁸ While its mechanism of action is unclear, it is suggested that SAM-e may normalize levels of specific neurons in the brain,⁹ and support brain bioenergetics.¹⁰

Other nutrients that impact neurotransmitters have been closely studied for their possible applications in treating depression. L-tryptophan, for example, is a precursor to serotonin, and is now available again in the United States as a dietary supplement ingredient, after contaminated L-trytophan was linked to serious health issues in the late 1980s. Its efficacy and safety were reviewed by a team from the University of Freiburg, Germany, who reported L-tryptophan is suitable for treating mild forms of depression and also benefits sleep; they added improved purification and analytic methods support the safety of L-tryptophan, which also has a low level of side effects in comparison to pharma antidepressants.¹¹ L-tryptophan’s efficacy has been established in clinical trials, including a recent trial in healthy women, which found L-tryptophan induces a positive bias in emotional interactions, similar to that of serotonergic antidepressants.¹²

5-Hydroxy-L-tryptophan (5-HTP) is the immediate precursor to L-tryptophan and has been a popular choice in mood enhancing dietary supplements. Studies show it is well-absorbed from oral dosing, easily crosses the blood-brain barrier and effectively increases central nervous system synthesis of serotonin, working to address conditions such as depression and anxiety.¹³ Further, it appears to be extremely safe, with no definitive cases of toxicity reported.¹⁴ Researchers from the Portland VA Medical Center, Ore., suggested adding 5-HTP to SSRI antidepressant treatment may have synergistic effects, working to impact both serotonin uptake and synthesis.¹⁵

A proprietary extract of Griffonia simplicifolia seed (as Serotain™, from Triarco) has been studied as a natural 5-HTP source. Mark Anderson, Ph.D., director of research and development, Triarco, noted the proprietary formula is safe and efficacious. “Research shows Serotain elevates mood by making serotonin more available to the body,” he said. “Serotain helps to balance mood and suppress appetite, making it ideal for consumers looking to control cravings when dieting and for those experiencing depression or anxiety.”

Another interesting amino acid with a role to play in the natural antidepressant market is L-theanine, a free amino acid found almost exclusively in tea plants. Studies suggest L-theanine increases brain levels of serotonin, dopamine and GABA (gamma aminobutyric acid), a key inhibitory neurotransmitter , and can exert neuroprotective effects and cognitive enhancement.¹⁶ It may even help protect dopamine neurons against neurotoxicity, such as that seen in Parkinson’s disease.¹⁷ Dutch researchers reported in healthy adults, ingestion of 50 mg of L-theanine could increase alpha wave activity, relaxing and focusing the brain without inducing drowsiness.¹⁸ Another clinical trial out of Japan found oral ingestion of L-theanine prior to an acute mental stress challenge decreased anxiety measures, possibly by inhibiting cortical neuron excitation.¹⁹

The idea of relaxing via a glass of warm milk before bed gave rise to research into milk protein hydrolysate; the ingredient, now available as Lactium®, from Pharmachem, contains a bioactive deca-peptide with relaxing properties. “Lactium helps control stress and regulate its effects on the body, as well as enhance emotional well-being,” Skop said. “It has been the subject of several clinical studies that have shown it to be safe, without side effects and effective at regulating the major symptoms of stress on the digestive and cardiovascular systems, as well as enhancing social, emotional and intellectual capabilities.”

French researchers examined the long-term effects of Lactium on mental stress in low- and high-stress responder women (n=27).²⁰ After 11 and 31 days of intervention, Lactium helped reduce the stress response, particularly in high-responder women. A similar study examined the effects of Lactium on females with stress-related symptoms.²¹ Sixty-three female volunteers, suffering from at least one stress-related disorder such as anxiety, sleep problems and general fatigue, randomly received either Lactium (150 mg/d) or a placebo for 30 days. Women taking Lactium had significantly greater improvement in stress symptoms.

Another clinical trial involved healthy subjects who ingested three times, 12 hours apart, two capsules of 200 mg Lactium or placebo, and then subjected to mental and physical stress tests.²² Subjects taking Lactium had significant decreases in plasma cortisol concentrations and blood pressure, compared to placebo subjects, during the stress tests, suggesting the compound exerted an anxiolytic effect.

References:

1. Soczynska JK et al. “Acetyl-L-carnitine and alpha-lipoic acid: possible neurotherapeutic agents for mood disorders?” Expert Opin Investig Drugs. 2008 Jun;17(6):827-43.

2. “Acetyl-L-carnitine.” Altern Med Rev. 1999 Dec;4(6):438-41.

3. Rossini M et al. “Double-blind, multicenter trial comparing acetyl l-carnitine with placebo in the treatment of fibromyalgia patients.” Clin Exp Rheumatol. 2007 Mar-Apr;25(2):182-8.

4. Zanardi R, Smeraldi E. “A double-blind, randomised, controlled clinical trial of acetyl-L-carnitine vs. amisulpride in the treatment of dysthymia.” Eur Neuropsychopharmacol. 2006 May;16(4):281-7. Epub 2005 Nov 28.

5. Shea TB. “Effects of dietary supplementation with N-acetyl cysteine, acetyl-L-carnitine and S-adenosyl methionine on cognitive performance and aggression in normal mice and mice expressing human ApoE4.” Neuromolecular Med. 2007;9(3):264-9.

6. Papakostas GI, Alpert JE, Fava M. “S-adenosyl-methionine in depression: a comprehensive review of the literature.” Curr Psychiatry Rep. 2003 Dec;5(6):460-6.

7. Mischoulon D, 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-61S.

8. Di Rocco A et al. “S-Adenosyl-Methionine improves depression in patients with Parkinson's disease in an open-label clinical trial.” Mov Disord. 2000 Nov;15(6):1225-9.

9. Genedani S et al. “Influence of SAMe on the modifications of brain polyamine levels in an animal model of depression.” Neuroreport. 2001;12(18):3939-42.

10. Silveri MM et al. “S-adenosyl-L-methionine: effects on brain bioenergetic status and transverse relaxation time in healthy subjects.” Biol Psychiatry. 2003;54(8):833-9.

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