Fight Depression with 5-HTP

Serotonin May Improve Your Outlook

Fight Depression with 5-HTP
Avoiding this dark affliction may help prevent dementia
By Will Block

Keep your face to the sunshine and
you cannot see the shadow.

— Helen Keller

ince you’re reading this, you obviously survived the recent holidays. Congratulations! We hope they were a joyous time for you and your loved ones. Alas, that is not true for many people, who react badly to Christmas and its attendant festivities. Paradoxically, the season of renewed hope for peace on earth and goodwill toward men, of giving and sharing, of families coming together and celebrating the best in human nature, makes some people fall into depression. Far from being imbued with the uplifting Christmas spirit, they feel sad, alienated, and gloomy.

Don’t Be SAD

The same feelings can afflict people who have the condition called seasonal affective disorder (SAD), which is just a pretentious name for what used to be called winter depression. As that name suggests, this condition (which afflicts women more than men) occurs in winter, when the days are short—the shortest of all coming just four days before Christmas—and the weather may be cold and bleak, with gray skies and not a flower in sight. (Those of you who live in Palm Beach or Palm Springs probably have no idea what we’re talking about—sorry.)

Many people react badly to such climatic conditions and become depressed. Their symptoms, which include apathy, overeating, and poor or excessive sleep, as well as a general sadness and perhaps irritability, seldom rise (or should we say sink) to the level of clinical depression, but they can be severe enough to impair the victim’s functional ability in daily life. And some cases do degenerate into real depression; they may even lead to thoughts of suicide.*

*Never ignore anyone’s hints at suicide. They are a cry for help that may be desperately needed, so get professional help! It is not true that people who talk about suicide don’t carry through with it. On the contrary, most people who do it had talked about it.

The main cause of winter depression appears to be light deprivation caused by the shortened period of daylight during the winter months. Indeed, the symptoms tend to disappear as the days grow longer in the spring, and they can often (but not always) be alleviated during the winter by increased exposure to sunlight or to very bright artificial light. But why? Scientists believe the condition has something to do with a disruption in the brain’s balance between the neurotransmitter serotonin and the hormone melatonin (which plays a vital role in sleep regulation); this balance is known to be sensitive to the day/night cycle, which affects the secretion of melatonin by the pineal gland.

Depression Can Lead to Other Diseases . . .

It doesn’t take a psychiatrist to tell you that depression is bad for your health—this has been common knowledge throughout human history. Modern science, however, has provided measurable evidence of it, as well as some plausible explanations for how a bad state of mind can cause temporary or even lasting harm to the physical body, including the brain itself.

Such harm can come in the form of chronic diseases, such as diabetes (for which the most important risk factor is obesity—see the sidebar), heart disease, Alzheimer’s disease, and perhaps cancer. Furthermore, depression can compromise the integrity of our immune system, making us more susceptible to acute diseases, such as colds, flu, or other kinds of infection. And, of course, it can cause significant functional disability (including sexual dysfunction), making it difficult to perform the normal activities of daily living and to engage in routine social activities.

Could 5-HTP Help Curb Your Appetite?

As with depression, a common symptom of stress is overeating. Food is not only omnipresent, but it’s always comforting, providing sensory pleasure even when our capacity to enjoy many of the other pleasures of life has been eroded by stress. So we overeat … and gain weight … and feel guilty … which heightens our stress (or depression) … and so we keep overeating …

Can this vicious cycle be interrupted? Perhaps. Researchers at MIT have been investigating the neurophysiological basis for behaviors such as this for many years. Recently their attention was focused on 5-HTP, which can help alleviate depression and which may be able to inhibit stress-induced overeating. They investigated a vexing question related to the action of 5-HTP on the brain: is orally administered 5-HTP effective without assistance from an agent (called a decarboxylase inhibitor) that can protect it from destruction in the bloodstream?1

Despite the undoubted ability of 5-HTP to affect brain function by enhancing serotonin levels, it had been believed that this effect is limited by the conversion of 5-HTP to serotonin in the bloodstream, before it has a chance to cross the blood-brain barrier (serotonin is found in relatively high concentrations in blood platelets, and also in the intestinal wall). And since serotonin, unlike 5-HTP, cannot cross the blood-brain barrier, the serotonin made in our blood does not get into our brains. Thus, the reasoning went, if we wish to maximize 5-HTP’s effect on brain serotonin levels, we should take 5-HTP together with a decarboxylase inhibitor, which inhibits this in-the-blood conversion to serotonin.

The MIT researchers questioned this assumption. Using six healthy young women (average age 27) who had fasted overnight, they measured the effects of administering just 5-HTP (100 or 150 mg), without a decarboxylase inhibitor, on the blood levels of this compound over a 24-hour period. They found that the women’s blood levels of 5-HTP almost tripled within 1 hour and declined back to the baseline values in 24 hours.

Fine, but what about the women’s brain levels of 5-HTP? The only way to obtain that information is to remove the brains, homogenize them in a blender, and subject them to chemical analysis. Believe it or not, every one of the six volunteers refused to allow the researchers to do that, so they had to make do with laboratory rats instead.

They found, first of all, that 5-HTP alone (not taken orally but injected intraperitoneally) raised the rats’ blood levels of this substance by up to 12 times, compared to control rats injected with saline solution, and their brain levels of 5-HTP increased by up to 4 times. It should be noted, however, that the doses used were enormous, being 50 to 167 times greater, on a body-weight basis, than those used for the women. Thus, it’s not clear how relevant the comparison really is.

In any case, the researchers also found that these huge doses of 5-HTP significantly curbed the appetite of rats that had been food-deprived or that were under stress (from a tail-pinching clamp). Although the striking differences between the human and rat experiments in this study left major questions unanswered, the researchers speculated, “Since oral 5-HTP given without a decarboxylase inhibitor elevates plasma [blood] 5-HTP levels in humans, it is conceivable that this amino acid might be useful in diminishing the overeating and perhaps other symptoms sometimes associated with stress.”

For actual evidence of the possible role of 5-HTP in appetite suppression in humans, see “Lose Weight with 5-HTP and EGCG” (April 2003). The research described there was carried out in Italy with very large doses (up to 900 mg/day) of 5-HTP.

  1. Amer A, Breu J, McDermott J, Wurtman RJ, Maher TJ. 5-Hydroxy-L-tryptophan suppresses food intake in food-deprived and stressed rats. Pharmacol Biochem Behav 2004;77:137-43.

. . . And Vice Versa

Isn’t that depressing? Furthermore, as would be self-evident to a child, having a chronic disease can cause depression, thus contributing to what may become a downward spiral to poorer and poorer health, both mentally and physically. When it comes to depression and chronic disease, it’s not a chicken-or-egg question, but rather a matter of chicken and egg: each one is definitely a setup for the other. So the thing to do is avoid them both. That’s easier said than done, but it’s also true that it may be easier to do with the help of certain nutritional supplements than without them.

5-HTP Helps Elevate Your Mood

It has been known for years that the natural amino acid 5-hydroxytryptophan, or 5-HTP, is helpful in improving the mood of people afflicted with mild to moderate depression.1 The reason is well understood: 5-HTP is the direct precursor to serotonin, the neurotransmitter most directly involved in the regulation of mood, as well as of other manifestations of our state of mind, such as appetite, libido, and sleep (serotonin is itself a precursor to the sleep hormone, melatonin).

Deficiencies in brain serotonin levels can disrupt the patterns of neural activity that govern these conditions and that usually keep them within normal, healthy limits. Such deficiencies are most commonly caused by stress and aging, and they can lead to depressed, anxious, irritable, impulsive, or abusive behavior; they can also cause insomnia and headaches. The good news, though, is that serotonin deficiency can often be rectified by supplementation with 5-HTP. This compound, which is produced naturally in our bloodstream and our brains from the dietary amino acid tryptophan, is not found in our food but is extracted from the African plant Griffonia simplicifolia.

Depression and Dementia—in Denmark?

Considering that depression is a disease of the brain, it may not be too surprising that one of its consequences is an increased risk for another brain disease: dementia. That is the sobering conclusion reached by researchers at the University of Copenhagen, who decided to investigate this question using hospital admission statistics in Denmark.2 Specifically, they sought to determine whether the number of prior admissions for patients hospitalized for depression or bipolar disorder* was predictive of an increased risk for being hospitalized in the future with a diagnosis of dementia.

*Also called manic-depressive illness or manic depression, bipolar disorder is a disease in which, for no apparent reason, the patient’s mood and behavior alternate between the extremes of mania (a kind of exaggerated and unfounded elation) and depression, usually in cycles of months or years.

Because hospital admission occurs only in serious cases of a given condition, this criterion was judged to be better proof of a correct diagnosis than the more subjective criteria that might otherwise be invoked. Thus, the researchers believed that their results would be more reliable than those of previous studies, some of which had found an apparent cause-and-effect between depression and dementia, and some of which had not.

Yes—Depression Increases the Risk for Dementia

The researchers examined the medical records of 18,726 patients (67% women, average age 58) who had been hospitalized at least once with depression, and 4248 patients (59% women, average age 52) who had been hospitalized at least once with bipolar disorder, during the period 1986 to 1999. They found that the number of prior hospital admissions for either depression or bipolar disorder significantly increased the risk of being diagnosed with dementia at a subsequent hospital admission. Specifically, the rate of dementia increased on average by 13% for every prior admission for depression, and by 6% for every prior admission for bipolar disorder.

Using the term “affective disorder” to encompass both depression and bipolar disorder, the researchers concluded,

The study supports the possibility of a direct association between affective disorder and dementia … and further supports the hypothesis that affective episodes may cause permanent affection of the brain … If our results can be confirmed in future studies, they underscore the importance of early and sustained prophylaxis [preventive treatment] of the evolving process of the illness in depressive and bipolar disorders.

In other words: to help prevent Alzheimer’s disease, it’s wise to try hard to prevent depression and bipolar disorder, and to treat them aggressively if they show signs of occurring. In the nutritional supplement arena, 5-HTP is well known for its ability to help lift the clouds of anxiety and depression; and for bipolar disorder, the medical treatment of choice is the mineral lithium.* It has been known for half a century that lithium can successfully treat this condition, and there is growing evidence that it may also provide some degree of protection against the brain damage characteristic of neurodegenerative diseases, such as Alzheimer’s.

*Regarding 5-HTP, see, e.g., “Alleviating Anxiety with 5-HTP Is Good for Your Heart” (April 2001), “5-HTP Can Lift Your Spirits” (March 2002), and “5-HTP May Reduce Your Risk for Disease” (April 2004). And regarding lithium, see “Can Lithium Benefit Brain Health?” (June 2004).

Hey, Baby, What’s Your Color?

As this magazine is being mailed, it is midwinter, and the days have been getting longer for the past month or so. But they’re still pretty short, and the weather is still cold (except where it’s not). So thank God for Valentine’s Day, when the rosy glow of love can warm our hearts and, for a while, banish some of the winter blues that may have settled in. If you have a loved one afflicted by winter depression, you might try giving the gift of 5-HTP (not instead of, but in addition to, something sweet and romantic—let’s not forget our priorities!) to help turn that blue color to a nice, cheery pink.


  1. Shaw K, Turner J, Del Mar C. Tryptophan and 5-hydroxytryptophan for depression (Cochrane Review). In: The Cochrane Library, Issue 4, 2001. Oxford: Update Software.
  2. Kessing LV, Andersen PK. Does the risk of developing dementia increase with the number of episodes in patients with depressive disorder and in patients with bipolar disorder? J Neurol Neurosurg Psychiatry 2004;75: 1662-6.

Will Block is the publisher and editorial director of Life Enhancement magazine.

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