Serotonin deficiency signs/symptoms:
* Depressed
* Nervous/anxious
* Worrier
* Fears/phobias
* Negative/pessimistic
* Irritable/impatient/edgy
* Obsessive compulsive tendency
* Think about the same things over & over again
* Self destructive, masochistic or suicidal thoughts/plans
* Low self esteem/confidence
* Anger/rage/explosive behavior/assaultive
* Sleep problems/light sleeper
* Crave sugar/carbohydrates/alcohol/marijuana
o Use these substances to improve mood & relax
* Feel worse in and dislike dark weather
* Chronic pain (e.g. headaches, backaches, fibromyalgia)
* PMS
* Antidepressants or 5-HTP improve mood
* Family history of depression/anxiety/OCD/eating disorders
Serotonin levels may be low due to a combination of genetic and acquired reasons. Serotonin can be raised effectively using either nutrient based therapies or medications. Serotonin is synthesized from the amino acid tryptophan.
Factors which reduce serotonin levels:
* Stress
* PCB’s, pesticides and plastic chemicals exposure
* Under-methylation
* Inadequate sunlight exposure
* Tryptophan (precursor) deficiency
* Iron, calcium, magnesium, zinc, B3, B6, folate & vitamin C deficiency
* Inadequate sleep
* Glutathione deficiency
* Chronic infections
* Food allergies
* Genetic serotonin receptor abnormalities
* Chronic opioid, alcohol, amphetamine & marijuana use
* Human growth hormone deficiency
* Progesterone deficiency
* Impaired blood flow to brain
* Insulin resistance or deficiency
Take tryptophan supplements to boost serotonin levels. Tryptophan supplements have been proven by experts to help raise serotonin deficiency levels. The body cannot manufacture its own tryptophan. In the body, tryptophan is converted to 5-HTP which is in turn converted to serotonin. If you cannot buy tryptophan supplements, take 5-HTP supplements or eat foods high in tryptophan through out the day like turkey, nuts, brown rice, and fish.
The Many Faces of Serotonin
Deficiency Linked to GI Disorders, Depression, Asthma and Fibromyalgia
By Chris D. Meletis, ND
Tell A Friend Printer friendly version
Serotonin is a neurotransmitter often connected to mood. However, while serotonin deficiency is linked to depression, its role in a host of other conditions often goes unrecognized by the general public. Yet, serotonin deficiency is the common denominator in the etiology of a number of other disorders such as irritable bowel syndrome and asthma. Furthermore, serotonin deficiency is linked to sleep disturbances, migraines, fatigue, carbohydrate cravings, and obesity.
Under normal conditions, neurons in the brain release serotonin to carry messages to other neurons: for example, to alter some aspect of mood, appetite, confidence, or sleep. Serotonin is then returned to the parent neuron to be reused for signaling. In people with low serotonin levels, however, the available serotonin is recaptured too quickly, leaving it insufficient time to adequately activate the adjacent neuron and allow the signal to sufficiently continue along the neural network. This can result in a number of disorders.
In this article, I will discuss both serotonin’s role in well-being and the many other ways serotonin affects our health.
Mood Elevator
Targeting serotonin’s vital role in brain chemistry, pharmaceutical companies have developed a class of drugs called selective serotonin reuptake inhibitors (SSRIs). As their name suggests, SSRIs inhibit the reuptake of serotonin, allowing it to remain in the synaptic gaps between neurons for longer so that enough of the hormone builds up to trigger nerve impulses.
The fact that SSRIs were originally prescribed for treating depression but are now widely taken for treating related disorders of serotonin deficit such as insomnia, migraine, fibromyalgia, and IBS confirms serotonin’s wide-reaching role in the body. However, as popular as the SSRIs have been, they have not been without serious side effects such as nausea, irritability, sexual dysfunction, daytime sedation, insomnia, dry mouth, and tremor, and a heightened risk of suicidal thoughts in children and adolescents.1 (See the article “SSRIs Plus NSAIDs: A Potentially Lethal Combination,” available on the website.)
Far-Reaching Effects of Serotonin
Given serotonin’s diverse actions, a deficiency in this neurotransmitter has a far greater impact beyond depression and is increasingly linked with a wide range of health problems. Manifestation of some of these disorders—specifically, insomnia, weight-control issues, fatigue or loss of energy, and reduced ability to concentrate—is, in fact, used by the American Psychiatric Association for diagnosing major depression.2
Impact on Sleep
Sleep disturbances feature strongly in depression, with insomnia reported by more than 90 percent of depressed patients.3 Altered sleep patterns in depression occur in the phase of sleep associated with memory known as random eye movement (REM) sleep and are considered a marker for major depression. Even in healthy subjects, serotonin deficiency significantly decreases the time spent in both REM sleep and non-REM (deep sleep) and prolongs wakefulness.
In insomnia patients, increasing brain serotonin levels can overcome serotonin depletion’s negative impact on sleep continuity.4 Researchers also believe that complete relief of insomnia may improve the prognosis for depression.3
Emotional Eating
Serotonin also is known to affect appetite, especially for carbohydrates. Low levels of the amino acid tryptophan, a precursor to serotonin in the body, have been linked to binge eating and carbohydrate cravings that lead to unwanted weight gain.5 Tryptophan competes with large neutral amino acids for transport across the blood-brain barrier. Studies have shown that the plasma tryptophan ratio to other amino acids in obese patients is well below normal, suggesting a serotonin deficiency.6
To overcome this deficit, insulin released when carbohydrates are consumed facilitates the removal of competing amino acids from the serum into muscle, thus allowing tryptophan to enter the brain more easily and increase brain serotonin levels.7 As a result, obese people frequently consume carbohydrates over other food types to overcome low tryptophan intake into the brain and achieve “feel good” levels of serotonin. Boosting serotonin levels in the brain therefore creates a feeling of satiety to suppress appetite.
In clinical trials, increasing brain serotonin levels reduces caloric intake in obese or overweight patients8-9 who have been seen to lose weight in these studies despite making no conscious effort to do so.8-9 Overweight diabetic patients also have reduced brain serotonin levels compared with healthy controls.10 Restoring brain serotonin levels in these patients normalizes eating behavior by reducing energy intake from carbohydrates and fats, reducing body weight.10
Headaches
Serotonin is implicated as a key neurotransmitter in migraines. According to epidemiological studies, both migraines and depression are connected11 since the body’s serotonin levels fall during a migraine attack.12 Studies have shown that replenishing brain serotonin levels can relieve migraine as effectively as a standard migraine drug13 and reduce the need for analgesic therapy in patients with chronic tension-type headaches14 due to serotonin’s ability to relax muscles and control the dilation of blood vessels.
Fibromyalgia
Since serotonin is an inhibitory neurotransmitter that calms the nervous system to relieve tension and anxiety, its deficiency is thought to be the reason for the lowering of the pain threshold that occurs in fibromyalgia patients.15
SSRIs are commonly used for treating fibromyalgia, a condition characterized by generalized joint and muscle pain and tenderness in certain parts of the body, but with no manifestation of physical abnormality. Patients with fibromyalgia may also experience stiffness, sleep disturbances, irritable bowel syndrome, temperomandibular joint syndrome, and menstrual disorders. Low serotonin levels in these patients have been inversely correlated with clinical measures of perceived pain.16-17
Researchers have also found that fibromyalgia and migraines commonly occur together18 given their common etiology of low serotonin levels. Furthermore, low serotonin levels are seen in other chronic pain syndromes such as painful diabetic neuropathy and chronic fatigue syndrome.
Irritable Bowel Syndrome
Found abundantly in the digestive system, serotonin is known to influence bowel function. Since most of the serotonin produced in the body is made in the gastrointestinal tract, a serotonin deficiency increases vulnerability to digestive tension, constipation, and irritable bowel syndrome (IBS).
Specialized serotonin-releasing cells in the gastric mucosa are present throughout the digestive system. Serotonin is a powerful smooth muscle stimulant and an important regulator of gut motility.19 In fact, the enteric nervous system (ENS) is often referred to as a second brain since serotonin appears to be the common link in gastrointestinal motility, intestinal secretion, and pain perception between the ENS and the central nervous system.20
Researchers have identified several serotonin (5-HT) receptor subtypes, of which 5-HT3 and 5-HT4 have been found to be the most important for regulating gastrointestinal function.19 Once activated, 5-HT4 receptors modulate peristaltic neurotransmission by facilitating the release of several neurotransmitters, the net result of which is forward movement of contents through the gastrointestinal tract.21
Respiratory Difficulties
In people with asthma, depression and anxiety are strongly associated with decreased pulmonary control, including more visits to the doctor or emergency room, inability to do usual activities, and more days of symptoms compared with those who do not have depression or anxiety.22 Those with asthma are also more than twice as likely than those without the disease to have current depression, a lifetime diagnosis of depression, and anxiety.22
In addition, emotional problems and depression in childhood have been found to increase the vulnerability to developing asthma in early adulthood.23 Improving depression in patients with asthma therefore has a significant impact since greater depressive symptom severity scores are associated with lower asthma-related quality of life.24
Naturally Elevating Serotonin
When investigating natural alternatives to alleviate serotonin deficiency, researchers take into account that serotonin cannot cross the blood-brain barrier and must be synthesized in the brain itself. Fortunately, tryptophan and its metabolite 5-hydroxytryptophan (5-HTP), from which serotonin is made, can and do cross the blood-brain barrier.
Tryptophan is an essential amino acid found in small amounts in high-protein foods. It is uniquely responsible for serotonin synthesis in the body, using cofactors such as vitamin B6, magnesium, and vitamin C, to facilitate this conversion. Unfortunately, even a normal diet all too frequently does not provide the quantities of tryptophan required since it is the least abundant amino acid found in food. It is believed that the brain receives less than 1 percent of tryptophan from a typical diet as its use is diverted to metabolic functions such as producing various body tissue proteins and vitamin B3 synthesis and it faces tough competition from other amino acids to cross the blood-brain barrier. Modern-day diets, with their emphasis on fast foods and carbohydrates, also make serotonin synthesis more difficult.
Another way to generate higher serotonin levels is to consume its direct precursor 5-HTP, which is made from tryptophan in the body. Unlike tryptophan, 5-HTP absorption is less affected by other amino acids and it cannot be shunted into protein production. Both SSRIs and 5-HTP increase serotonin availability in the brain, but in different ways. SSRIs recycle serotonin, keeping it circulating in the brain for longer, whereas 5-HTP synthesizes new serotonin to replenish depleted levels in the central nervous system.
In a six-week study, 5-HTP was found to be as effective for depression as a common antidepressant drug, but with fewer and less severe side effects than the drug.25 5-HTP also has been shown to relieve anxiety,26 enhance sleep,4 suppress appetite,10 prevent migraines,13 and support the health of fibromyalgia patients.27
Conclusion
Serotonin affects much more than mood. The multifaceted health consequences of serotonin deficiency are based on its complex functions as a neurotransmitter. Adequate brain levels of serotonin are therefore critical for promoting feelings of well-being, satiety, and relaxation.
Ensuring healthy serotonin levels is also important during aging. Excessive tryptophan degradation occurs in aging bodies as a result of increased activity of tryptophan-degrading enzymes, which can cause declining serotonin levels.28 Maintaining optimal serotonin levels can therefore provide important physical and emotional health benefits across all age groups.
References
1. Available at: http://www.fda.gov/bbs/topics/news/2004/new01124.html. Accessed October 29, 2008.
2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: APA, 1994.
3. Thase ME. Antidepressant treatment of the depressed patient with insomnia. J Clin Psychiatry. 1999;60 (Suppl. 17):28-31.
4. Riemann D, Vorderholzer U. Treatment of depression and sleep disorders. Significance of serotonin and L-tryptophan in pathophysiology and therapy. Fortschr Med. 1998 Nov;116(32):40-42.
5. Gendall KA, Joyce PR. Meal-induced changes in tryptophan:LNAA ratio: effects on craving and binge eating. Eat Behav. 2000 Sep;1(1):53-62.
6. Breum L, Rasmussen MH, Hilsted J, Fernstrom JD. Twenty-four-hour plasma tryptophan concentrations and ratios are below normal in obese subjects and are not normalized by substantial weight reduction. Am J Clin Nutr. 2003 May;77(5):1112-1118.
7. Wurtman RJ, Wurtman JJ. Brain serotonin, carbohydrate-craving, obesity and depression. Obes Res. 1995 Nov;3(Suppl):477S-480S.
8. Ceci F, Cangiano C, Cairella M, et al. The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects. J Neural Transm 1989;76(2):109-117.
9. Cangiano C, Ceci F, Cascino A, et al. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. Am J Clin Nutr 1992 Nov;56(5):863-867.
10. Cangiano C, Laviano A, Del Ben M, et al. Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients. Int J Obes Relat Metab Disord. 1998 Jul;22(7):648-654.
11. Breslau N, Davis GC, Schultz LR, Peterson EL. Joint 1994 Wolff Award Presentation. Migraine and major depression: a longitudinal study. Headache. 1994 Jul-Aug;34(7):387-393.
12. Selmaj K. Blood serotonin level in sciatica and the serotonin theory of migraine pathogenesis. Neurol Neurochir Pol. 1979 Mar;13(2):169-172.
13. Titus F, Dávalos A, Alom J, Codina A. 5-Hydroxytryptophan versus methysergide in the prophylaxis of migraine. Randomized clinical trial. Eur Neurol. 1986;25(5):327-329.
14. Ribeiro CA. L-5-Hydroxytryptophan in the prophylaxis of chronic tension-type headache: a double-blind, randomized, placebo-controlled study. For the Portuguese Head Society. Headache. 2000 Jun;40(6):451-456.
15. Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998 Aug;3(4):271-280.
16. Hrycaj P, Stratz T, Muller W. Platelet 3Himipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome. J Rheumatol. 1993;20:1986-1988. [letter]
17. Russell IJ, Michalek JE, Vipraio GA, et al. Platelet 3H-imipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome. J Rheumatol 1992;19:104-109.
18. Nicolodi M, Sicuteri F. Fibromyalgia and migraine, two faces of the same mechanism. Serotonin as the common clue for pathogenesis and therapy. Adv Exp Med Biol. 1996;398:373-379.
19. Fayyaz M, Lackner JM. Serotonin receptor modulators in the treatment of irritable bowel syndrome. Ther Clin Risk Manag. 2008 Feb;4(1):41-48.
20. Gershon MD. The enteric nervous system: a second brain. Hosp Pract (Minneap). 1999 Jul 15;34(7):31-32,35-38,41-42 passim.
21. Grider JR. Desensitization of the peristaltic reflex induced by mucosal stimulation with the selective 5-HT4 agonist tegaserod. Am J Physiol Gastrointest Liver Physiol. 2006 Feb;290(2):G319-G327.
22. Strine TW, Mokdad AH, Balluz LS, Berry JT, Gonzalez O. Impact of depression and anxiety on quality of life, health behaviors, and asthma control among adults in the United States with asthma, 2006. J Asthma. 2008 Mar;45(2):123-133.
23. Goodwin RD, Sourander A, Duarte CS, et al. Do mental health problems in childhood predict chronic physical conditions among males in early adulthood? Evidence from a community-based prospective study. Psychol Med. 2008 May 28:1-11 [Epub ahead of print].
24. Brown ES, Murray M, Carmody TJ, et al. The Quick Inventory of Depressive Symptomatology-Self-report: a psychometric evaluation in patients with asthma and major depressive disorder. Ann Allergy Asthma Immunol. 2008 May;100(5):433-438.
25. Poldinger W, Calanchini B, Schwarz W. A functional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine. Psychopathology. 1991;24:53-81.
26. Kahn RS, Westenberg HG. L-5-hydroxytryptophan in the treatment of anxiety disorders. J Affect Disord. 1985 Mar-Apr;8(2):197-200.
27. Puttini PS, Caruso I. Primary fibromyalgia and 5-hydroxy-L-tryptophan: a 90 day open study. J Int Med Res. 1992;20:182-189.
28. Kepplinger B, Baran H, Kainz A, et al. Age-related increase of kynurenic acid in human cerebrospinal fluid - IgG and beta2-microglobulin changes. Neurosignals. 2005;14(3):126-135.
* Depressed
* Nervous/anxious
* Worrier
* Fears/phobias
* Negative/pessimistic
* Irritable/impatient/edgy
* Obsessive compulsive tendency
* Think about the same things over & over again
* Self destructive, masochistic or suicidal thoughts/plans
* Low self esteem/confidence
* Anger/rage/explosive behavior/assaultive
* Sleep problems/light sleeper
* Crave sugar/carbohydrates/alcohol/marijuana
o Use these substances to improve mood & relax
* Feel worse in and dislike dark weather
* Chronic pain (e.g. headaches, backaches, fibromyalgia)
* PMS
* Antidepressants or 5-HTP improve mood
* Family history of depression/anxiety/OCD/eating disorders
Serotonin levels may be low due to a combination of genetic and acquired reasons. Serotonin can be raised effectively using either nutrient based therapies or medications. Serotonin is synthesized from the amino acid tryptophan.
Factors which reduce serotonin levels:
* Stress
* PCB’s, pesticides and plastic chemicals exposure
* Under-methylation
* Inadequate sunlight exposure
* Tryptophan (precursor) deficiency
* Iron, calcium, magnesium, zinc, B3, B6, folate & vitamin C deficiency
* Inadequate sleep
* Glutathione deficiency
* Chronic infections
* Food allergies
* Genetic serotonin receptor abnormalities
* Chronic opioid, alcohol, amphetamine & marijuana use
* Human growth hormone deficiency
* Progesterone deficiency
* Impaired blood flow to brain
* Insulin resistance or deficiency
Take tryptophan supplements to boost serotonin levels. Tryptophan supplements have been proven by experts to help raise serotonin deficiency levels. The body cannot manufacture its own tryptophan. In the body, tryptophan is converted to 5-HTP which is in turn converted to serotonin. If you cannot buy tryptophan supplements, take 5-HTP supplements or eat foods high in tryptophan through out the day like turkey, nuts, brown rice, and fish.
The Many Faces of Serotonin
Deficiency Linked to GI Disorders, Depression, Asthma and Fibromyalgia
By Chris D. Meletis, ND
Tell A Friend Printer friendly version
Serotonin is a neurotransmitter often connected to mood. However, while serotonin deficiency is linked to depression, its role in a host of other conditions often goes unrecognized by the general public. Yet, serotonin deficiency is the common denominator in the etiology of a number of other disorders such as irritable bowel syndrome and asthma. Furthermore, serotonin deficiency is linked to sleep disturbances, migraines, fatigue, carbohydrate cravings, and obesity.
Under normal conditions, neurons in the brain release serotonin to carry messages to other neurons: for example, to alter some aspect of mood, appetite, confidence, or sleep. Serotonin is then returned to the parent neuron to be reused for signaling. In people with low serotonin levels, however, the available serotonin is recaptured too quickly, leaving it insufficient time to adequately activate the adjacent neuron and allow the signal to sufficiently continue along the neural network. This can result in a number of disorders.
In this article, I will discuss both serotonin’s role in well-being and the many other ways serotonin affects our health.
Mood Elevator
Targeting serotonin’s vital role in brain chemistry, pharmaceutical companies have developed a class of drugs called selective serotonin reuptake inhibitors (SSRIs). As their name suggests, SSRIs inhibit the reuptake of serotonin, allowing it to remain in the synaptic gaps between neurons for longer so that enough of the hormone builds up to trigger nerve impulses.
The fact that SSRIs were originally prescribed for treating depression but are now widely taken for treating related disorders of serotonin deficit such as insomnia, migraine, fibromyalgia, and IBS confirms serotonin’s wide-reaching role in the body. However, as popular as the SSRIs have been, they have not been without serious side effects such as nausea, irritability, sexual dysfunction, daytime sedation, insomnia, dry mouth, and tremor, and a heightened risk of suicidal thoughts in children and adolescents.1 (See the article “SSRIs Plus NSAIDs: A Potentially Lethal Combination,” available on the website.)
Far-Reaching Effects of Serotonin
Given serotonin’s diverse actions, a deficiency in this neurotransmitter has a far greater impact beyond depression and is increasingly linked with a wide range of health problems. Manifestation of some of these disorders—specifically, insomnia, weight-control issues, fatigue or loss of energy, and reduced ability to concentrate—is, in fact, used by the American Psychiatric Association for diagnosing major depression.2
Impact on Sleep
Sleep disturbances feature strongly in depression, with insomnia reported by more than 90 percent of depressed patients.3 Altered sleep patterns in depression occur in the phase of sleep associated with memory known as random eye movement (REM) sleep and are considered a marker for major depression. Even in healthy subjects, serotonin deficiency significantly decreases the time spent in both REM sleep and non-REM (deep sleep) and prolongs wakefulness.
In insomnia patients, increasing brain serotonin levels can overcome serotonin depletion’s negative impact on sleep continuity.4 Researchers also believe that complete relief of insomnia may improve the prognosis for depression.3
Emotional Eating
Serotonin also is known to affect appetite, especially for carbohydrates. Low levels of the amino acid tryptophan, a precursor to serotonin in the body, have been linked to binge eating and carbohydrate cravings that lead to unwanted weight gain.5 Tryptophan competes with large neutral amino acids for transport across the blood-brain barrier. Studies have shown that the plasma tryptophan ratio to other amino acids in obese patients is well below normal, suggesting a serotonin deficiency.6
To overcome this deficit, insulin released when carbohydrates are consumed facilitates the removal of competing amino acids from the serum into muscle, thus allowing tryptophan to enter the brain more easily and increase brain serotonin levels.7 As a result, obese people frequently consume carbohydrates over other food types to overcome low tryptophan intake into the brain and achieve “feel good” levels of serotonin. Boosting serotonin levels in the brain therefore creates a feeling of satiety to suppress appetite.
In clinical trials, increasing brain serotonin levels reduces caloric intake in obese or overweight patients8-9 who have been seen to lose weight in these studies despite making no conscious effort to do so.8-9 Overweight diabetic patients also have reduced brain serotonin levels compared with healthy controls.10 Restoring brain serotonin levels in these patients normalizes eating behavior by reducing energy intake from carbohydrates and fats, reducing body weight.10
Headaches
Serotonin is implicated as a key neurotransmitter in migraines. According to epidemiological studies, both migraines and depression are connected11 since the body’s serotonin levels fall during a migraine attack.12 Studies have shown that replenishing brain serotonin levels can relieve migraine as effectively as a standard migraine drug13 and reduce the need for analgesic therapy in patients with chronic tension-type headaches14 due to serotonin’s ability to relax muscles and control the dilation of blood vessels.
Fibromyalgia
Since serotonin is an inhibitory neurotransmitter that calms the nervous system to relieve tension and anxiety, its deficiency is thought to be the reason for the lowering of the pain threshold that occurs in fibromyalgia patients.15
SSRIs are commonly used for treating fibromyalgia, a condition characterized by generalized joint and muscle pain and tenderness in certain parts of the body, but with no manifestation of physical abnormality. Patients with fibromyalgia may also experience stiffness, sleep disturbances, irritable bowel syndrome, temperomandibular joint syndrome, and menstrual disorders. Low serotonin levels in these patients have been inversely correlated with clinical measures of perceived pain.16-17
Researchers have also found that fibromyalgia and migraines commonly occur together18 given their common etiology of low serotonin levels. Furthermore, low serotonin levels are seen in other chronic pain syndromes such as painful diabetic neuropathy and chronic fatigue syndrome.
Irritable Bowel Syndrome
Found abundantly in the digestive system, serotonin is known to influence bowel function. Since most of the serotonin produced in the body is made in the gastrointestinal tract, a serotonin deficiency increases vulnerability to digestive tension, constipation, and irritable bowel syndrome (IBS).
Specialized serotonin-releasing cells in the gastric mucosa are present throughout the digestive system. Serotonin is a powerful smooth muscle stimulant and an important regulator of gut motility.19 In fact, the enteric nervous system (ENS) is often referred to as a second brain since serotonin appears to be the common link in gastrointestinal motility, intestinal secretion, and pain perception between the ENS and the central nervous system.20
Researchers have identified several serotonin (5-HT) receptor subtypes, of which 5-HT3 and 5-HT4 have been found to be the most important for regulating gastrointestinal function.19 Once activated, 5-HT4 receptors modulate peristaltic neurotransmission by facilitating the release of several neurotransmitters, the net result of which is forward movement of contents through the gastrointestinal tract.21
Respiratory Difficulties
In people with asthma, depression and anxiety are strongly associated with decreased pulmonary control, including more visits to the doctor or emergency room, inability to do usual activities, and more days of symptoms compared with those who do not have depression or anxiety.22 Those with asthma are also more than twice as likely than those without the disease to have current depression, a lifetime diagnosis of depression, and anxiety.22
In addition, emotional problems and depression in childhood have been found to increase the vulnerability to developing asthma in early adulthood.23 Improving depression in patients with asthma therefore has a significant impact since greater depressive symptom severity scores are associated with lower asthma-related quality of life.24
Naturally Elevating Serotonin
When investigating natural alternatives to alleviate serotonin deficiency, researchers take into account that serotonin cannot cross the blood-brain barrier and must be synthesized in the brain itself. Fortunately, tryptophan and its metabolite 5-hydroxytryptophan (5-HTP), from which serotonin is made, can and do cross the blood-brain barrier.
Tryptophan is an essential amino acid found in small amounts in high-protein foods. It is uniquely responsible for serotonin synthesis in the body, using cofactors such as vitamin B6, magnesium, and vitamin C, to facilitate this conversion. Unfortunately, even a normal diet all too frequently does not provide the quantities of tryptophan required since it is the least abundant amino acid found in food. It is believed that the brain receives less than 1 percent of tryptophan from a typical diet as its use is diverted to metabolic functions such as producing various body tissue proteins and vitamin B3 synthesis and it faces tough competition from other amino acids to cross the blood-brain barrier. Modern-day diets, with their emphasis on fast foods and carbohydrates, also make serotonin synthesis more difficult.
Another way to generate higher serotonin levels is to consume its direct precursor 5-HTP, which is made from tryptophan in the body. Unlike tryptophan, 5-HTP absorption is less affected by other amino acids and it cannot be shunted into protein production. Both SSRIs and 5-HTP increase serotonin availability in the brain, but in different ways. SSRIs recycle serotonin, keeping it circulating in the brain for longer, whereas 5-HTP synthesizes new serotonin to replenish depleted levels in the central nervous system.
In a six-week study, 5-HTP was found to be as effective for depression as a common antidepressant drug, but with fewer and less severe side effects than the drug.25 5-HTP also has been shown to relieve anxiety,26 enhance sleep,4 suppress appetite,10 prevent migraines,13 and support the health of fibromyalgia patients.27
Conclusion
Serotonin affects much more than mood. The multifaceted health consequences of serotonin deficiency are based on its complex functions as a neurotransmitter. Adequate brain levels of serotonin are therefore critical for promoting feelings of well-being, satiety, and relaxation.
Ensuring healthy serotonin levels is also important during aging. Excessive tryptophan degradation occurs in aging bodies as a result of increased activity of tryptophan-degrading enzymes, which can cause declining serotonin levels.28 Maintaining optimal serotonin levels can therefore provide important physical and emotional health benefits across all age groups.
References
1. Available at: http://www.fda.gov/bbs/topics/news/2004/new01124.html. Accessed October 29, 2008.
2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: APA, 1994.
3. Thase ME. Antidepressant treatment of the depressed patient with insomnia. J Clin Psychiatry. 1999;60 (Suppl. 17):28-31.
4. Riemann D, Vorderholzer U. Treatment of depression and sleep disorders. Significance of serotonin and L-tryptophan in pathophysiology and therapy. Fortschr Med. 1998 Nov;116(32):40-42.
5. Gendall KA, Joyce PR. Meal-induced changes in tryptophan:LNAA ratio: effects on craving and binge eating. Eat Behav. 2000 Sep;1(1):53-62.
6. Breum L, Rasmussen MH, Hilsted J, Fernstrom JD. Twenty-four-hour plasma tryptophan concentrations and ratios are below normal in obese subjects and are not normalized by substantial weight reduction. Am J Clin Nutr. 2003 May;77(5):1112-1118.
7. Wurtman RJ, Wurtman JJ. Brain serotonin, carbohydrate-craving, obesity and depression. Obes Res. 1995 Nov;3(Suppl):477S-480S.
8. Ceci F, Cangiano C, Cairella M, et al. The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects. J Neural Transm 1989;76(2):109-117.
9. Cangiano C, Ceci F, Cascino A, et al. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. Am J Clin Nutr 1992 Nov;56(5):863-867.
10. Cangiano C, Laviano A, Del Ben M, et al. Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients. Int J Obes Relat Metab Disord. 1998 Jul;22(7):648-654.
11. Breslau N, Davis GC, Schultz LR, Peterson EL. Joint 1994 Wolff Award Presentation. Migraine and major depression: a longitudinal study. Headache. 1994 Jul-Aug;34(7):387-393.
12. Selmaj K. Blood serotonin level in sciatica and the serotonin theory of migraine pathogenesis. Neurol Neurochir Pol. 1979 Mar;13(2):169-172.
13. Titus F, Dávalos A, Alom J, Codina A. 5-Hydroxytryptophan versus methysergide in the prophylaxis of migraine. Randomized clinical trial. Eur Neurol. 1986;25(5):327-329.
14. Ribeiro CA. L-5-Hydroxytryptophan in the prophylaxis of chronic tension-type headache: a double-blind, randomized, placebo-controlled study. For the Portuguese Head Society. Headache. 2000 Jun;40(6):451-456.
15. Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998 Aug;3(4):271-280.
16. Hrycaj P, Stratz T, Muller W. Platelet 3Himipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome. J Rheumatol. 1993;20:1986-1988. [letter]
17. Russell IJ, Michalek JE, Vipraio GA, et al. Platelet 3H-imipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome. J Rheumatol 1992;19:104-109.
18. Nicolodi M, Sicuteri F. Fibromyalgia and migraine, two faces of the same mechanism. Serotonin as the common clue for pathogenesis and therapy. Adv Exp Med Biol. 1996;398:373-379.
19. Fayyaz M, Lackner JM. Serotonin receptor modulators in the treatment of irritable bowel syndrome. Ther Clin Risk Manag. 2008 Feb;4(1):41-48.
20. Gershon MD. The enteric nervous system: a second brain. Hosp Pract (Minneap). 1999 Jul 15;34(7):31-32,35-38,41-42 passim.
21. Grider JR. Desensitization of the peristaltic reflex induced by mucosal stimulation with the selective 5-HT4 agonist tegaserod. Am J Physiol Gastrointest Liver Physiol. 2006 Feb;290(2):G319-G327.
22. Strine TW, Mokdad AH, Balluz LS, Berry JT, Gonzalez O. Impact of depression and anxiety on quality of life, health behaviors, and asthma control among adults in the United States with asthma, 2006. J Asthma. 2008 Mar;45(2):123-133.
23. Goodwin RD, Sourander A, Duarte CS, et al. Do mental health problems in childhood predict chronic physical conditions among males in early adulthood? Evidence from a community-based prospective study. Psychol Med. 2008 May 28:1-11 [Epub ahead of print].
24. Brown ES, Murray M, Carmody TJ, et al. The Quick Inventory of Depressive Symptomatology-Self-report: a psychometric evaluation in patients with asthma and major depressive disorder. Ann Allergy Asthma Immunol. 2008 May;100(5):433-438.
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