Can neurotrophins, or anything else, aid romance?

Making Love Last
with Better Nutrition

By Will Block

Love is a complex neurobiological phenomenon that depends on the right mixture of trust, belief, pleasure, and reward activities within the brain’s limbic system. The processes governed by the limbic system involve serotonergic, vasopressin, dopamine, and oxytocin signaling.1

A step above ordinary love is Romantic love which can be defined as “a state of intense longing for union with another.”2 The first stage of romantic love usually involves intense emotional reactions. Among these are euphoria, intensely focused attention on the preferred individual, obsessive thought about the person, and emotional dependency on and craving for emotional union with the beloved person.

The Study of Human Attachments

Since the dawn of humans, “love’s intensity” has been portrayed by modalities such as cave paintings, clay figures, story-telling, music, dance, and poetry. These have not been scientifically quantifiable. Until now. With the use of scientific animal model studies, other aspects of love have been uncovered involving cellular, neural, and endocrine mechanisms implicated in maternal care and pair bonding.

As professor Ruth Feldman, PhD has written in a very recent issue of Trends in Cognitive Sciences:3 “Those [model studies] gave rise to a new field of inquiry—the neurobiology of human attachments—which integrates insights from other mammals with new tools available for human research—brain imaging, neuroendocrinology, genetics and epigenetics, and peptide administration—to test the biological basis of human attachments.”

Pleasure Ability

Fulfilling or pleasurable activities are required for survival and appetitive motivational systems, usually governing beneficial biological behaviors like eating, sex, and reproduction.1 Indeed, a broad basis of common signaling and beneficial neurobiological features exists with connection to love, thereby combining physiological aspects related to maternal, romantic or sexual love and attachment with other healthy activities or neurobiological states. Dietary supplementation can make use of this understanding, and feed into mind/ body or integrative medicine.

Stress-Reduction and Health-Promotive Potential of Love

Love, pleasure, and lust have a stress-reducing and health-promoting potential, since they carry the ability to heal or facilitate beneficial motivation and behavior.

In addition, love and pleasure ensure the survival of individuals, not to mention the human race. After all, love is a joyful and useful activity that encompasses wellness and feelings of well-being.

We have written about a number of ways to enhance love.

Serotonergic (5-HTP)

See “5-HTP Saves Romance” in the August 2011 issue of this publication. The consequences of lovesickness and separation have only recently come to the increased attention of medical investigations. In part, this may be due to discomfort and embarrassment concerning revealing or admitting to lovesickness.

Victims of love loss frequently ignore the side effects.4 They don’t give the matter sufficient consciousness. This often results in insomnia, the inability to concentrate, restlessness, and anxiety. Other negative consequences include sadness and depression, changes in appetite and eating behavior, impairment of the autonomic nervous system, increased alcohol consumption or alcohol abuse, and many others. With psychotherapy, it is usually possible to determine the cause of these side effects and work through the pain. Alternatively, and especially as the result of the Italian study, it is possible for individuals to dampen their lovesickness by providing their bodies with natural substances that can have a positive effect on the biochemical processes taking place.

5-HTP Can Help Heal Heartbreak

A new open-label trial, conducted at the University of Pavia in Italy (where else?), evaluated the clinical efficacy of 5-HTP, a natural serotonin precursor, in 15 young, healthy subjects with high levels of romantic stress.4 The subjects were not clinically depressed. Serotonin is a principal inhibitory neurotransmitter, biochemically derived from tryptophan, an amino acid that is also a precursor to serotonin. It can also be derived, more directly, from 5-HTP. Serotonin is a well-known contributor to feelings of well-being, and consequently has been a primary target for antidepressant drugs. The ideas behind these drugs involves slowing serotonin breakdown, extending its stay in the synapses of the brain, and reducing its uptake.

Starting with the knowledge that neurotrophins—growth factors that induce neuron survival, development, and function—and serotonin both have been linked to romantic attachment in humans, the researchers sought to measure changes in the levels of a particular neurotrophin, brain-derived neurotrophic factor (BDNF). At the same time, the researchers examined platelet serotonin content in relation to the changes in romantic stress throughout the study.

All of the 15 subjects (11 females and 4 males, with a mean age of 23.3 ± 2.1 years) had experienced either a recent romantic break-up or reported recent romantic problems. Participants were treated openly for 6 weeks with 12.8 mg of 5-HTP, along with 1.1 mg of vitamin B1 and 1.4 mg of vitamin B6, all taken twice daily.

Love, pleasure, and lust have a stress-
reducing and health-promoting
potential, since they carry the ability
to heal or facilitate beneficial
motivation and behavior.

BDNF and platelet serotonin content were determined at baseline, at 3 weeks, and after the completion of the 6-week trial. Also, after 3 weeks and at the end of the 6-week trial the subjects were evaluated using an adapted version of a questionnaire developed by the Dr. Inge Seiffge-Krenke, a developmental psychologist who has written about coping with stress in different phases of romantic development.

Romantic Stress Reduction

There were significant improvements in romantic stress scores from weeks 0 through 3, but not from weeks 3 through 6. Yet at 6 weeks, the subjects were found to have both higher BDNF and platelet serotonin values. This indicated that direct modulation of the serotonergic system with the 5-HTP and B vitamins formulation is likely to be beneficial for young subjects with high levels of acute romantic stress, reducing the psychological suffering associated with unreciprocated, terminated, or some other romantic love problem. The findings suggest that this approach by itself could be an effective alternative treatment for patients who prefer a nutritional approach to drugs or psychotherapy.

Love is a joyful and useful activity
that encompasses wellness and
feelings of well-being.

The Importance of BDNF for Romantic Attachment

The Italian study also found that subjects with romantic stress display deficiencies in their serotonergic function and plasma levels of BDNF, and that supplementation with 5-HTP and B vitamins reversed these biochemical changes. In fact, these changes correlate closely with the changes in romantic stress. This demonstrates that the serotonin system is likely to play a major role in the psychobiology of love, as well as in social bonding. Especially noteworthy is recent research showing that BDNF plays a role in romantic attachment, the establishment of a relationship between two sexual partners.5

In other research, negative mood states were found to be associated with a reduced expression of BDNF.6 Negative moods are a sure-fire way to cool a romantic relationship. A prior study showed that BDNF could serve as a marker for the action of psychopharmacological agents such as antidepressants7—exactly what was found in the current study, albeit with nutrients instead of drugs.

Even though the Italian study was small and open-label, rather than the gold standard randomized double-blind, placebo controlled type, the significant response seen in subjects strongly suggests that modifying the serotonergic system with even small amounts of supplements may be quite useful for subjects with high levels of romantic stress. While larger studies are needed to confirm these preliminary findings, the existence of strong anecdotal evidence is reassuring.

Previous observations have implied that serotonergic dysfunction may be involved in human romantic stress and that increasing the activity of the serotonergic system may have use for the treatment of psychological suffering associated with the end of romantic love. Because this is an area of considerable concern in a world in which an increasingly high value is placed on love, there is hope that more definitive research is on the way.

DHEA significantly increased
the frequency of sexual thoughts,
sexual interest, and satisfaction with
both mental and physical aspects of
sexuality. The researchers concluded
that DHEA improves well-being and
sexuality in women with
adrenal insufficiency.

Adrenal System (DHEA)

See “The DHEAging of Romance” in the February 2013 issue. In this article, a German study published in the New England Journal of Medicine in 1999 is referenced. In it researchers investigated the physiologic role of DHEA in patients with adrenal insufficiency.8

This study was randomized and double-blinded, and followed 24 women with adrenal insufficiency who received 50 mg of DHEA or placebo orally each morning for four months, with a one-month washout period, and then the DHEA and the placebo were reversed. DHEA raised the initially low serum concentrations of DHEA, DHEA’s sulfate form (DHEAS), androstenedione, and testosterone into the normal range, while serum concentrations of sex hormone-binding globulin, total cholesterol, and high-density lipoprotein cholesterol (HDL) decreased significantly, probably due to an androgenic effect.

Also, DHEA significantly increased the frequency of sexual thoughts, sexual interest, and satisfaction with both mental and physical aspects of sexuality. The researchers concluded that DHEA improves well-being and sexuality in women with adrenal insufficiency.

PEA has been linked neurologically
with the euphoria of the early stages
of romantic love (hence the
nickname), and it’s found, perhaps
not coincidentally, in chocolate.

Our current knowledge of the neurobiology of romantic love remains scanty. In view of the complexity of a sentiment like love, it would not be surprising that a diversity of biochemical mechanisms could be involved in the mood changes of the initial stage of a romance. In the present study, the researchers examined whether the early romantic phase of a loving relationship could be associated with alterations in circulating levels of neurotrophins (NTs).

I’m in the Mood for Love

See “I’m in the Mood for Love” in the November 2012 issue. Plasma levels of neural growth factors (NGF), brain-derived neurotrophins (BDNF), and other neurothrophins (such as NT-3 and NT-4) were measured in a total of 58 subjects who had recently fallen in love and compared with those of two control groups, consisting of subjects who were either single or were already engaged in a long-lasting relationship.4

The NGF levels were significantly higher in the subjects who were newly-in-love in than in either the subjects with a long-lasting relationship or the subjects with no relationship.

Notably, there was also a significant positive correlation between levels of NGF and the intensity of romantic love as assessed with the passionate love scale. No differences in the concentrations of other NTs were detected. In 39 subjects in love who-after 12-24 months maintained the same relationship but were no longer in the same mental state to which they had referred during the initial evaluation, plasma NGF levels decreased and became indistinguishable from those of the control groups. Taken together, these findings suggest that some behavioral and/or psychological features associated with falling in love could be related to raised NGF levels in the bloodstream.

Phenylalanine Can Be Converted into a Love Molecule

In an article published in August of 2008 in Life Enhancement, “Phenylalanine May Cheer You Up,” the amino acid named in the title seems to improve mood in depressed patients by conversion to the “love molecule.” In this article we wrote, “Sometimes we’re not happy, and if that condition is severe enough and lasts long enough, it’s called depression.”

A susceptibility to depression has hung like a black cloud over mankind throughout history. During that time, men and women have applied endless ingenuity toward finding remedies that work. Some of them do work—sometimes, for some people. It’s an iffy proposition, and the challenge remains almost as great as ever. The advent of antidepressant drugs in modern times has been an undeniable blessing, but it’s one with some unpleasant strings attached.

Enter Phenylalanine

A more natural approach is to use nutritional supplements, which many people prefer because they’re largely free of adverse side effects, and they’re less expensive, too. The amino acid phenylalanine has long been of interest because of its role in the production of dopamine and noradrenaline, two neurotransmitters that play key roles in the regulation of mood, especially with regard to our sense of well-being, i.e., our happiness. Significantly, deficiencies of these neurotransmitters in the brain are associated with depression.

Phenylethylamine—The Hidden Asset

It’s significant that the administration of supplemental dopa (deoxy-phenylalanine), which lies between tyrosine and dopamine in the metabolic pathway, produces no antidepressant effects. This suggests that supplemental tyrosine may exert its effects not via dopa and the catecholamines, but instead via its conversion in the opposite direction, to phenylalanine (this is allowed by the laws of chemistry).9

But how could phenylalanine exert antidepressant effects? Well, phenylalanine is the precursor to a psychoactive compound you may have heard of: phenylethylamine, aka the “love molecule.” In the brain, phenylethylamine (PEA for short) acts as a neuromodulator—a compound that influences the actions of neurotransmitters—in this case, dopamine and noradrenaline.

Love’s neurobiological mechanisms
are also discussed in the light of
medicine and health (read it again),
and be sure to try
the supplements referenced.

Thus, even if phenylalanine and tyrosine don’t affect the levels of dopamine or noradrenaline via the tyrosine pathway—and we don’t know for sure whether they do or not—they may indirectly affect the activity of these neurotransmitters via the PEA pathway.10 (Perhaps both mechanisms are involved.)

Although plasma levels of phenylalanine and PEA are correlated, dietary intake of phenylalanine appears to have no short-term (overnight) effect on PEA levels.11 This is probably a reflection of the multiple metabolic pathways that phenylalanine can take, which dilute its short-term effects on any given metabolite. In the longer term, however, the effect of phenylalanine on PEA levels can be seen.

Of Romance and Chocolate

In the laboratory, PEA is the precursor to a great variety of other psychoactive compounds, including neurotransmitters, hormones, stimulants, antidepressants, and hallucinogens. One such derivative is amphetamine, and PEA’s pharmacological properties are, in fact, similar to those of amphetamine.12 (Remember, though, that PEA is made naturally in the brain and elsewhere in the body, in small, safe quantities.)

PEA has been linked neurologically with the euphoria of the early stages of romantic love (hence the nickname), and it’s found, perhaps not coincidentally, in chocolate. (It’s also found in oil of bitter almonds, which is not quite as popular as chocolate on Valentine’s Day.) This discovery led to the “chocolate theory of love,” but the theory doesn’t hold much water, alas, because dietary PEA is so quickly metabolized by the enzyme monoamine oxidase-B in the blood that hardly any of it can get through to the brain.*

* For more on phenylethylamine, see the sidebar in the May 2007 issue, “It’s Good to Be PEA-Brained” in the article “Chocolate for Longer and Happier Life.”

Be Positive!

A very important part of being happy—and healthy and in love—is to maintain a positive attitude, no matter what. That’s easier said than done, of course, and if you could use a little help along the way, a phenylalanine formulation might be just the thing to lift your spirits. If it works for you, that’s great. Scientists would love to know exactly how it works. But it doesn’t really matter, does it?

What an interesting phenomenon love is!

Almost everybody can relate to a state of “being or falling in love” even though it is difficult to define love. In addition, depending on the background or “current state” we get a vast number of variant answers to our questions about love. Following common knowledge, love is a strong, passionate affection for a person.

Hence, the Oxford English Dictionary defines love as an intense feeling of deep affection or fondness for a person or a thing, a sexual passion, or sexual relations, in general. Thus, love is an emotion often associated with consensual sexual activity, or the willing, and even eager, participation of the individuals involved.

However, only recently has the biology of love, and in particular its neurobiological aspects, become a focus of basic science as this review attests. Medical, or health, implications related to the love physiology are still speculative, i.e., mainly not proven. Although at first it may sound logical that love—given its biological function to ensure the survival of a species via social attachment, gathering, copulation and reproduction—is a phylogenetically healthy activity, neurobiological research has only started to examine the possible mechanisms underlying this assumption and its consequences for the individual organism and associated ontogenetic health outcomes and benefits. In this report, evidence for common neurobiological pathways underlying the love phenomenon is found. Love’s neurobiological mechanisms are also discussed in the light of medicine and health (read it again), and be sure to try the supplements referenced.


  1. Esch T, Stefano GB. The Neurobiology of Love. Neuro Endocrinol Lett. 2005 Jun;26(3):175-92.
  2. Zou Z, Song H, Zhang Y, Zhang X. Romantic Love vs. Drug Addiction May Inspire a New Treatment for Addiction. Front Psychol. 2016 Sep 22;7:1436.
  3. Feldman R. The Neurobiology of Human Attachments. Trends Cogn Sci. 2017 Feb;21(2):80-99.
  4. Emanuele E, Bertona M, Minoretti P, Geroldi D. An open-label trial of L 5-hydroxytryptophan in subjects with romantic stress. Neuro Endocrinol Lett. 2010;31(5):663-6.
  5. Marazziti D, Roncaglia I, Del Debbio A, Bianchi C, Massimetti G, Origlia N, Domenici L, Piccinni A, Dell’Osso L. Brain derived neurotrophic factor in romantic attachment. Psychol Med. 2009;39:1927-30.
  6. Castrén E, Rantamäki T. Role of brain-derived neurotrophic factor in the aetiology of depression: implications for pharmacological treatment. CNS Drugs. 2010 Jan 1;24(1):1-7.
  7. Wang JW, Dranovsky A, Hen R. The when and where of BDNF and the antidepressant response. Biol Psychiatry. 2008 Apr 1;63(7):640-1.
  8. Arlt W, Callies F, van Vlijmen JC, Koehler I, Reincke M, Bidlingmaier M, Huebler D, Oettel M, Ernst M, Schulte HM, Allolio B. Dehydroepiandrosterone replacement in women with adrenal insufficiency. N Engl J Med. 1999 Sep 30;341(14):1013-20.
  9. Kravitz HM, Sabelli HC, Fawcett J. Dietary supplements of phenylalanine and other amino acid precursors of brain neuroamines in the treatment of depressive disorders. J Am Osteopath Assoc. 1984;S4/1Suppl:119-123.
  10. Pogson CI, Knowles RG, Salter M. The control of aromatic amino acid catabolism and its relationship to neurotransmitter amine synthesis. Crit Rev Neurobiol. 1989;5(1):29-64.
  11. Davis BA, O’Reilly RL, Placatka CL, Paterson A, Yu PH, Durden DA. Effect of dietary phenylalanine on the plasma concentrations of phenylalanine, phenylethylamine, and phenylacetic acid in healthy volunteers. Prog Neuro-Psychopharmacol Biol Psychiat. 1991;15:611-23.
  12. Janssen PA, Leysen JE, Megens AAHP, Awouters FHL. Does phenylethylamine act as an endogenous amphetamine in some patients? Int J Neuropsychopharmacol. 1999;2:229-40.

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

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