Specialty Supplements Target Depression

Major Depressive Disorder is a widespread disease that has been around for centuries. The ancient Greek physician Hippocrates described a syndrome of melancholia as a distinct disease with particular mental and physical symptoms. Depression spurred an entire music genre called the Blues and currently, depression is a household term. Depression can severely disrupt life, affecting the appetite, sleep, work and relationships.

According to the National Institute of National Health, Major Depressive Disorder is the leading cause of disability in the United States for people aged 15 to 44 years and affects approximately 14.8 million American adults, or about 6.7 percent of the U.S. population age 18 and older. Symptoms include persistent sad, anxious or empty feelings; feelings of hopelessness and/or pessimism; feelings of guilt, worthlessness and/or helplessness; irritability; restlessness; loss of interest in activities or hobbies; fatigue and decreased energy; difficulty concentrating, remembering details and making decisions; insomnia, early-morning wakefulness or excessive sleeping; overeating or appetite loss; thoughts of suicide; suicide attempts; and persistent aches or pains, headaches, cramps or digestive problems that do not ease even with treatment.

Depression has no single cause; often, it results from a combination of things such as family history, trauma and physical conditions.

The current economic situation can also bring about depression. People are worried about their jobs, losing their homes and tightening their budgets. Many people may also face higher medical costs due to cutting back on, or losing health insurance. This is all the more reason why consumers will be looking toward less costly alternatives to prescription medications, including natural remedies and dietary supplements. Plenty of products are finding their niche within this market as launches of new stress/sleep products in both the dietary supplement and the food and beverage industry are up from last year, according to the Global New Products Database (GNPD).

Ingredients from plants, amino acids and even cows can help reduce the symptoms of depression and get consumers back to their happy lives.

MOOOood Support

The time-honored tradition of drinking a glass of milk to get relaxed before bedtime has found its way into supplements to help reduce stress and anxiety. Numerous studies on alphaS1-casein hydrolysate (as Lactium, from Pharmachem Laboratories) have shown that it reduces systolic and diastolic blood pressure; decreases blood cortisol levels; reduces anxiety in rats; improves digestive, intellectual, social, cardiovascular and emotional problems related to stress; and improves sleep duration and efficiency, especially in subjects with moderate anxiety or depression.

Further studies suggest an antistress profile of a tryptic bovine alphaS1-casein hydrolysate in humans. Subjects, in a double blind study were randomly allocated to ingest either 200 mg of alphaS1-casein hydrolysate (TS) or bovine skimmed milk powder as a placebo (CS) three times, 12 hours apart.¹ Blood samples were taken before and after the subjects were submitted to stress tests. The stress tests increased systolic and diastolic blood pressures and heart rate. Results indicated lower both systolic and diastolic blood pressures in the TS. In addition, the results showed a significant decrease of plasma cortisol concentrations in the TS but not in the CS throughout the stress tests.

In women, alpha (s1)-casein hydrolysate decreased the stress-related symptoms in one study where 63 female volunteers suffering from at least one disorder that may be related to stress such as anxiety, sleep problems and general fatigue were randomly allocated to receive either tablets containing alpha (s1)-casein hydrolysate or placebo at the dose of 150 mg/d for 30 days.² Their symptoms were reduced particularly in digestion (P<0.01), cardiovascular (P<0.05), intellectual (P<0.01), emotional (P<0.05) and social problems (P<0.05).

Chocolate Stress Reliever

Consumers may want to add chocolate to their milk to help boost their mood. Or they may want to think about adding cacao to their diet. A French study looked at cocoa polyphenolic extract prepared from nonroasted cocoa beans containing high levels of flavonoids and their effect on rats undergoing the forced swimming test.³ It found cocoa polyphenolic extract significantly reduced the duration of immobility at both doses of 24 mg/kg/14 days and 48 mg/kg/14 days. The results of the forced swimming test after a subchronic treatment and after an additional locomotor activity test confirm the antidepressant-like effect of cocoa polyphenolic extract in the forced swimming test. Researchers suggest the effect might be related to cocoa polyphenol content. RFI Ingredients is currently in the midst of a clinical study involving Chocamine, a patented cocoa-based product that is intended to support energy, cognitive function and mood.

Mineral Mood Enhancers

Chromium is a mineral that humans require in trace amounts. It is an essential trace element involved in the metabolism of carbohydrates, lipids and proteins that acts by increasing the efficiency of insulin action. Chromium found in small quantities in foods such as brewer's yeast, calf liver, whole grains, processed meats and cheese. It can also be found in mood support supplements to help treat atypical depression. Atypical depression is associated with increased appetite and overeating during stressful situations.

In a double blind, multicenter, eight-week study, 113 adult outpatients with atypical depression were randomized 2:1 to receive 600 µg/d of elemental chromium (as chromium picolinate [CrPic], from Nutrition 21) or placebo.⁴ The CrPic group showed significant improvements from baseline compared with the placebo group for: appetite increase, increased eating, carbohydrate craving and diurnal variation of feelings. The CrPic patients had significantly greater response on total Hamilton Depression Rating Scale (HAM-D(21)) scores than the placebo group (65 percent vs. 33 percent; P<0.05) as well as significantly greater reductions of appetite increase, increased eating, carbohydrate craving and genital symptoms (e.g., level of libido). Chromium treatment was well-tolerated.

Another double blind, placebo-controlled, randomized clinical trial of CrPic in 14 patients with major atypical depression found the CrPic group improved their anxiety, hostility, interruptional sensitivity, paranoia and psychoticism.⁵

The alkaline earth metal magnesium is the ninth most abundant element in the universe by mass, but when a deficiency occurs within the human body, stress symptoms can surface, which can lead to increased risk of cardiovascular damage including hypertension, cerebrovascular and coronary constriction and occlusion, arrhythmias and sudden cardiac death.⁶ However, magnesium supplementation can reduce the occurrence of depression. Studies have shown a rapid recovery (less than seven days) from major depression using 125 to 300 mg of magnesium with each meal and at bedtime.⁷

PS Aide

Phosphatidylserine (PS) is a phospholipid component found in all cells and is most concentrated in the human brain. It is used as a universal building block for cell membranes, managing the cellular life processes. Studies have shown that PS (as SerinAid PS, from Chemi Nutra) can minimize some of the systemic effects of stress.⁸ One study found young adults with high neuroticism scores who took 300 mg/d of PS for a month felt less stressed and had a better mood.⁹ German researchers investigated the effect of PS on cognition and cortical activity after mental stress in 16 healthy subjects and found chronic supplementation of PS significantly decreased Beta-1 power in right hemispheric frontal brain regions (F8; P<0.05) before and after induced stress.¹⁰ The results for Beta-1 power in the PS group were connected to a more relaxed state compared to the controls.

Alpha to Omega-3

Omega-3 fatty acids are another good mood boosters, especially in women. A study published in early 2009 assessed multivariable-adjusted associations of fish consumption and dietary intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with depressive symptoms in 3,317 people during a 20-year period.¹¹ The highest quintiles of intakes of EPA (>/=0.03 percent energy), DHA (>/=0.05 percent energy) and EPA + DHA (>/=0.08 percent energy) were associated with a lower risk of depressive symptoms at year 10. The observed inverse associations were more pronounced in women, suggesting that dietary intakes of fish and long-chain omega-3 fatty acids may be inversely associated with chronic depressive symptoms in women. A 2008 study found middle-aged women who took enriched ethyl-EPA (E-EPA) supplementation for the treatment of psychological distress and depressive symptoms improved their episodes significantly more than those that took a placebo.¹²

It’s not just women who may become relaxed with increased intake of omega-3s. Substance abusers (n=22), both men and women, were assigned to either 3 g of omega-3 polyunsaturated fatty acids (PUFA), mainly EPA and DHA, or soybean oil in identically looking capsules.¹³ The trial was double blind, randomized and lasted three months. Assignment to n-3 PUFA treatment was accompanied by significant decreases in anger and anxiety scores compared to placebo assignment. These changes were associated with increases in plasma levels of both EPA and DHA monitored through blood tests, but an increase in EPA was more robustly correlated with low end-of-trial anxiety scores and an increase in DHA was more robustly correlated with low end-of-trial anger scores.

Impacting Neurotransmitters

Acetyl L-carnitine (ALC) is an orthomolecule that supports mitochondrial energy production and enhances the production of the neurotransmitter acetylcholine (Ach). A double blind, randomized, controlled clinical trial found that ALC was as effective as the antipsychotic drug amisulpride measured by total HAM-D(21) in patients with pure dysthymia (DSM IV).¹⁴ Patients (n=204) were randomized and treated with ALCAR 500 mg b.i.d. or amisulpride 50 mg u.i.d. for 12 weeks. A solid improvement of HAM-D(21) was observed in both treatment groups throughout the study. The results did not disclose statistically significant differences between treatments, but ALCAR was better tolerated.

Patients with fibromyalgia, a chronic syndrome characterized by widespread pain, troubled sleep, disturbed mood and fatigue may benefit from taking ALC to reduce pain and improve general and mental versus a placebo.¹⁵

Similarly, S-Adenosyl methionine (SAM-e) is a methyl donor that is involved in the synthesis of various neurotransmitters in the brain. Derived from the amino acid L-methionine through a metabolic pathway called the one-carbon cycle, SAM-e has been postulated to have antidepressant properties. A small number of clinical trials with parenteral or oral SAM-e have shown that, at doses of 200 to 1,600 mg/d, SAMe is superior to placebo and is as effective as tricyclic antidepressants in alleviating depression.¹⁶ In one study involving 20 HIV-seropositive individuals, diagnosed with Major Depressive Disorder, an eight-week intervention with SAM-e resulted in significant acute reduction in depressive symptoms, with effects evident as soon as the first week.¹⁷

Amino acids are critical to life and have a variety of roles in metabolism. One particularly important function is as the building blocks of proteins. Some amino acids can also help curb depressive symptoms. 5-Hydroxytryptophan (5-HTP) is one such amino acid. It is a precursor to the neurotransmitter serotonin. Serotonin plays an important role as in the modulation of anger, aggression, anxiety, mood, sleep, sexuality, appetite, pain sensation and metabolism. One study found 5-HTP to increase central nervous system (CNS) synthesis of serotonin.¹⁸ Therapeutic administration of 5-HTP was shown to be effective in treating a wide variety of conditions, including depression, fibromyalgia, binge eating associated with obesity, chronic headaches and insomnia. Also, it was well absorbed from an oral dose, with about 70 percent ending up in the bloodstream.

L-tryptophan has also been used to treat depression and sleep disorders. It is an essential amino acid that, like 5- HTP, is a biochemical precursor to serotonin. In Germany, researchers found L-tryptophan to be helpful for the treatment of mild forms of depression and in reestablishing a physiological sleep pattern in patients with chronic sleep problems.¹⁹ In another study of 115 patients, L-tryptophan was a more effective treatment for depression than placebo.²⁰

An amino acid found in green tea, L-theanine, has been shown to have relaxing effects.²¹ A Japanese study examined 12 participants who underwent four separate trials: one in which they took L-theanine at the start of an experimental procedure, one in which they took L-theanine midway, and two control trials in which they either took a placebo or nothing.²² The results showed L-theanine intake resulted in a reduction in the heart rate (HR) and salivary immunoglobulin A (s-IgA) responses to an acute stress task relative to the placebo group, thus it was suggested oral intake of L-theanine exerted an antistress effect.

Hormone Help

Melatonin is a naturally occurring hormone found in most animals, including humans and some other living organisms, including algae, that has a good potential for use as an antidepressant.²³ One study suggests melatonin can replace hypnotic drug therapy. Researchers examined sleep and behavioral disorders in 22 older adults (7 men and 15 women older than 65) and the facilitation of the discontinuation of regular hypnotic drugs with the supplement of melatonin in a prospective, randomized, double blind, placebo-controlled, crossover trial in a community-living population.²⁴ Participants had a history of sleep disorder complaints and 14 subjects were receiving hypnotic drug therapy. They received two months of melatonin (5 mg/d) and two months of placebo.

 Melatonin treatment for two months significantly improved sleep quality scores measured by a Northside Hospital Sleep Medicine Institute test (1.78+/-0.40) when compared with both basal (3.72+/-0.45; P=0.001) and placebo (3.44+/-0.56; P=0.025) groups. Depression measured by Geriatric Depression Scale and anxiety measured by the Goldberg Anxiety Scale also improved significantly after melatonin administration (P=0.043 and P=0.009, respectively). Nine out of 14 subjects receiving hypnotic drugs were able to discontinue this treatment during melatonin, but not placebo administration. In another trial, agomelatine, a synthetic form of melatonin, was found to be a promising and well-tolerated medication for the treatment of major depressive disorder.²⁵

Depression can be a debilitating disease, but formulators have myriad options when it comes to aiding consumers. Whether working with herbs, minerals, cocoa, amino acids or hormones, relief can be found from many ingredients.

References on the next page...

References for "Specialty Supplements Target Depression"

1. Messaoudi M. et al “Effects of a tryptic hydrolysate from bovine milk alphaS1-casein on hemodynamic responses in healthy human volunteers facing successive mental and physical stress situations.” Eur J Nutr. 2005 Mar;44(2):128-32. Epub 2004 Nov 2.

2. Kim JH et al. “Efficacy of alphas1-casein hydrolysate on stress-related symptoms in women.” Eur J Clin Nutr. 2007 Apr;61(4):536-41. Epub 2006 Nov 29.

3. Messaoudi M. et al. “Antidepressant-like effects of a cocoa polyphenolic extract in Wistar-Unilever rats.” Nutr Neurosci. 2008 Dec;11(6):269-76.

4. Docherty JP, et al. “A double-blind, placebo-controlled, exploratory trial of chromium picolinate in atypical depression: effect on carbohydrate craving” J Psychiatr Pract. 2005 Sep;11(5):302-14.

5. Davidson JR. et al. “Effectiveness of chromium in atypical depression: a placebo-controlled trial” Biol Psychiatry. 2003 Feb 1;53(3):261-4.

6. Seelig MS. “Consequences of magnesium deficiency on the enhancement of stress reactions; preventive and therapeutic implications (a review).” J Am Coll Nutr. 1994 Oct;13(5):429-46.

7. Eby GA, Eby KL. “Rapid recovery from major depression using magnesium treatment.” Med Hypotheses. 2006;67(2):362-70. Epub 2006 Mar 20.

8. Kelly GS. “Nutritional and botanical interventions to assist with the adaptation to stress.” Altern Med Rev. 1999 Aug;4(4):249-65.

9. Benton D. et al. “The influence of phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor” Nutr Neurosci. 2001;4(3):169-78.

10. Baumeister J. et al. “Influence of phosphatidylserine on cognitive performance and cortical activity after induced stress.” Nutr Neurosci. 2008 Jun;11(3):103-10.

11. Colangelo LA. et al. “Higher dietary intake of long-chain omega-3 polyunsaturated fatty acids is inversely associated with depressive symptoms in women. “ Nutrition. 2009 Feb 3. 12. Lucas M. et al. “Ethyl-eicosapentaenoic acid for the treatment of psychological distress and depressive symptoms in middle-aged women: a double-blind, placebo-controlled, randomized clinical trial.” Am J Clin Nutr. 2009 Feb;89(2):641-51. Epub 2008 Dec 30.13. Buydens-Branchey L, Branchey M, Hibbeln JR. “Associations between increases in plasma n-3 polyunsaturated fatty acids following supplementation and decreases in anger and anxiety in substance abusers.” Prog Neuropsychopharmacol Biol Psychiatry. 2008 Feb 15;32(2):568-75. Epub 2007 Nov 1.14. 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. 15. 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. 16. 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 Nov;76(5):1158S-61S. 17. Shippy RA. et al. “S-adenosylmethionine (SAM-e) for the treatment of depression in people living with HIV/AIDS.” BMC Psychiatry. 2004 Nov 11;4:38. 18. Birdsall TC “5-Hydroxytryptophan: a clinically-effective serotonin precursor.” Alt Med Rev. 1998 Aug;3(4):271-80.19. Riemann D, VorderholzerU. “[Treatment of depression and sleep disorders. Significance of serotonin and L-tryptophan in pathophysiology and therapy]”[Article in German]. Fortschr Med. 1998 Nov 20;116(32):40-2.20. Thomson J. et al. “The treatment of depression in general practice: a comparison of L-tryptophan, amitriptyline, and a combination of L-tryptophan and amitriptyline with placebo.” Psychol Med. 1982 Nov;12(4):741-51.21. Lu K. et al. “The acute effects of L-theanine in comparison with alprazolam on anticipatory anxiety in humans” Hum Psychopharmacol. 2004 Oct;19(7):457-65. 22. Kimura K. et al. “L-Theanine reduces psychological and physiological stress responses.” Biol Psychol. 2007 Jan;74(1):39-45. Epub 2006 Aug 22. 23. Detanico BC. et al. “Antidepressant-like effects of melatonin in the mouse chronic mild stress model.” Eur J Pharmacol. 2009 Feb 26. [Epub ahead of print] 24. Garzón C. “Effect of melatonin administration on sleep, behavioral disorders and hypnotic drug discontinuation in the elderly: a randomized, double-blind, placebo-controlled study.” Aging Clin Exp Res. 2009 Feb;21(1):38-42.25. Dolder CR, Nelson M, Snider M. “Agomelatine treatment of major depressive disorder.” Ann Pharmacother. 2008 Dec;42(12):1822-31. Epub 2008 Nov 25.