I’m in the Mood for Love

Alpha lipoic acid and acetyl L-carnitine can make you say …

… “simply” because of higher nerve growth factor levels 
-- By Will Block

Romantic love is the catalyst behind the spread of the human life. 
— E. Emanuele

A dominant portion of the human population is preoccupied with sex and love, although not necessarily in that order, or with the same emphasis (men tend to be more interested in sex and for women, it’s love). The fact remains that both of these “obsessions” are associated with health and longevity (see “Orgasm and Longevity: The Dose-Response Curve” in the March 1998 issue), and are thus worthy of our attention, not to mention acting as incentives for the cultivation of the art of love.

Unfortunately, while there is a growing body of knowledge about the biomechanics of sex, there is far, far less known about the neurobiology of romantic love, which for many is the sine qua non (an indispensable and essential condition) for sexual fulfillment. Unhappily, this is especially true for men; without libido, mechanics and expertise matter little.

Does biochemistry place an important role in love?

For scientists who have considered the complexity of love as a sentiment, it is clear that a range of biochemical mechanisms are involved in the mood alterations that mark the initial stage of a romance. So in a recent study,1 researchers at the Department of Health Sciences, Section of Psychiatry, University of Pavia, Pavia, Italy (where else would this be of such interest?) set out to examine the early star-struck phase of romantic relationships and determine whether this could be associated with changes in the intermingling levels of neurotrophins (NTs). NTs are a family of proteins that induce the survival, development, and function of neurons. Belonging to a class of growth factors that secrete proteins, NTs are proficient at signaling particular cells to survive, differentiate, and grow.

Without libido, mechanics and 
expertise matter little.

The researchers measured the plasma levels of 58 subjects who had recently fallen in love and compared them with two control groups, consisting of subjects who were either single or were already engaged in a long-lasting relationship. Measured were the neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and two explicit neurotrophins (NT-3 and NT-4).

The NGF level was significantly higher in the subjects newly-in-love [227 pg/ml*] than in either the subjects with a long-lasting relationship [123 pg/ml] or the subjects with no relationship [149 pg/ml]. 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 the NTs were detected, nor in BDNF.

* Picogram per milliliter (parts per trillion).

There was also a significant 
positive correlation between 
levels of NGF and the intensity of 
romantic love as assessed with 
the passionate love scale.

After 12–24 months, 39 of the subjects (out of the original 58 recruited) who were newly-in-love at the beginning of the study had maintained the same relationship. They were no longer in the same mental state to which they had referred during the initial evaluation: plasma NGF levels of the once newly-in-love had decreased and become 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 elevated NGF levels in the bloodstream. Could falling mean rising?

How to raise and empower NGF (and possibly your love quotient)

It has been know for nearly 25 years that acetyl L-carnitine (ALC) has been able to enhance cognitive performance (starting with aged rats), a measure of its effectiveness for age-related deficits.2 At the same time, NGF has been demonstrated to affect neuronal development and maintenance of the differentiated state in certain neurons of the peripheral and central nervous system of mammals.

ALC has been found to act in the brain as a metabolic cofactor in the synthesis of acetylcholine, a neurotransmitter directly associated with concentration and focus.3 ALC administration causes an increase in choline acetyltransferase† activity and an increase in NGF receptor expression in the striatum.§ The level of NGF in the hippocampus also increases. Another paper4 found that long term treatment with ALC completely prevents the loss of choline acetyltransferase activity in the CNS of aged rats, suggesting that ALC may rescue cholinergic pathways from age-associated degeneration due the diminished transport of NGF.

† Choline acetyltransferase is an enzyme that is synthesized within the body of a neuron. When transferred to the nerve terminal, its role is to join acetyl-CoA to choline, resulting in the formation of the neurotransmitter acetylcholine. 

§ The striatum is a subcortical (i.e., inside, rather than on the outside) part of the forebrain and the major input station of the basal ganglia system. The main components of the basal ganglia are the striatum, the globus pallidus, the substantia nigra, and the subthalamic nucleus. The largest component, the striatum, receives input from many brain areas but sends output only to other components of the basal ganglia.

Alpha-lipoic acid may treat erectile dysfunction

A recent study1 out of China investigated the mechanism of diabetic erectile dysfunction (ED) in order to find new ways to treat ED by detecting the changes in nitric oxide synthase (NOS) isoforms and the ED of diabetic rats through the administration of insulin and alpha-lipoic acid (ALA).

Fifty male rats were divided into Groups A (normal control, n=10), B (non-intervention diabetes mellitus, n=13), C (insulin intervention diabetes mellitus, n=12), and D (insulin + ALA intervention, n=15). Eight weeks later, the erectile function of the rats was assessed following apomorphine—a non-selective dopamine agonist used to treat movement disorders—injection and the NOS isoforms in the erectile tissues were measured.

All NOS isoforms are not alike

All the rats of Group A showed a normal erectile function (100%). In comparison, those in Groups B and C respectively exhibited a significantly decreased rate, 28.6% in Group B and 62.5% in Group C, but only 80.9% in Group D (insulin plus ALA). The numbers of positive nNOS fibers and eNOS in the penile tissues per visual field were 86.7 and 9.6 in Group A, but only 36.5 and 3.3 in Group B, 52.7 and 5.7 in Group C, and 71.4 and 7.4 in Group D (P < 0.05). However, the expression of iNOS was significantly lower in Group A (6.9) than in Groups B (43.6), C (36.2) and D (19.3) (P < 0.05). Compared with Groups B and C, the erectile function and the expressions of nNOS and eNOS were markedly increased, while the expression of iNOS significantly decreased in Group D (P < 0.05).

ALA is proved efficacious for 
diabetic erectile dysfunction, 
which might be related to its 
antioxidant effect, and this effect 
might hold up for pre-diabetics 
as well as non-diabetics.

Diabetes mellitus severely affects penile erectile function and the expressions of NOS isoforms in the cavernous tissues, for which hyperglycemia is mainly responsible. ALA is proved efficacious for diabetic ED, which might be related to its antioxidant effect, and this effect might hold up for pre-diabetics as well as non-diabetics.

Reference

  1. Yao LS, Wang YT, Chen Y, Dai YT. Expressions of NOS isoforms in the cavernous tissues of diabetic rat models. Zhonghua Nan Ke Xue 2009 Oct;15(10):915-9.

Plasma NGF levels of the 
once newly-in-love had decreased 
and became indistinguishable from 
those of the control groups.

Alpha lipoic acid can boost the power of NGF

In a study5 conducted at Queen Mary and Westfield College, in London, UK, researchers compared the effects of treatment of diabetic rats with either alpha-lipoic acid (ALA) at 100 mg/kg/day for 5 days/week or with recombinant human NGF at 0.2 mg/kg for 3 days/week. The goal was to examine the effects of the test materials on NGF-like immunoreactivity (NGFLI) and neuropeptide Y-like immunoreactivity (NPYLI) levels in the sciatic nerve and on the release of substance P-like immunoreactivity (SPLI) from the spinal cord in response to electrical stimulation of the dorsal roots in vitro. Immunoreactivity is the process in which an antigen and an antibody interact.

ALA can boost neurotrophic support 
in diabetic rats, with effects that 
include those related to NGF.

The diabetic rats showed depletion of NGFLI and NPYLI, together with reduced release of SPLI. Treatment with NGF increased the sciatic nerve NGFLI (to four times that seen in untreated diabetic rats) and normalized stimulus-evoked release of SPLI, but did not affect the sciatic nerve NPYLI. Treatment with ALA caused a small non-significant increase in sciatic nerve NGFLI, but normalized both NPYLI levels and stimulus-evoked release of SPLI. This indicates that ALA can boost neurotrophic support in diabetic rats, with effects that include those related to NGF. Can ALA boost the power of NGF in pre-diabetic or even non-diabetic subjects? Other evidence seems to indicate that it can.

Back to romance

Returning to the original premise—that raising NGF levels can increase the feelings of new love—consider the following, quoting Emanuele, 2006:

Intense romantic love, a complex sentiment typically directed toward a single person, is one of the most overwhelming of all affective states and has been the inspiration for some of the greatest achievements of mankind. As it typically involves emotional, cognitive, behavioural and erotic components, the functions of romantic love appear not to be limited to generate offsprings, but also to promote in individuals a stable emotional environment as well as to arise pleasant and safe feelings of happiness and sex arousal. The process of romantic love in humans begins with falling in love, a subjective experience characterized by intense focused attention on a preferred individual, obsessive thinking about him or her, emotional dependency on and craving for emotional union with this beloved, euphoria and increased energy. [References removed]

ALA is likely to boost to power of 
NGF in pre-diabetic or even 
non-diabetic subjects.

Then again, here is Emanuele, 2011: 6

Romantic love is the catalyst behind the spread of the human life. The neurobiology of love embraces the hypothesis that what we call “romantic attachment” or “romantic love” may be at least in part the expression of biological factors. A corollary of this hypothesis states that it is possible to learn much about the nature of human love by studying the molecules involved in the expression of social and affiliative behaviours. Under this theoretical framework, we have investigated the changes in plasma neurotrophin levels in subjects with early-stage romantic love. A positive association between the intensity of early romantic feelings and serum levels of nerve growth factor (NGF) has been identified. These findings link love with biologically relevant pathways for neuron survival and illuminate the biochemical correlates of such a complex feeling that so deeply affects our own lives. The progresses in the neurobiology of love suggest that this kind of research may open a new window onto our understanding of the very nature of human romantic bonding.

References

  1. Emanuele E, Politi P, Bianchi M, Minoretti P, Bertona M, Geroldi D. Raised plasma nerve growth factor levels associated with early-stage romantic love. Psychoneuroendocrinology 2006 Apr;31(3):288-94.
  2. Angelucci L, Ramacci MT, Taglialatela G, Hulsebosch C, Morgan B, Werrbach-Perez K, Perez-Polo R. Nerve growth factor binding in aged rat central nervous system: effect of acetyl-L-carnitine. J Neurosci Res 1988 Aug;20(4):491-6.
  3. De Simone R, Ramacci MT, Aloe L. Effect of acetyl-L-carnitine on forebrain cholinergic neurons of developing rats. Int J Dev Neurosci 1991;9(1):39-46.
  4. Taglialatela G, Navarra D, Cruciani R, Ramacci MT, Alemà GS, Angelucci L. Acetyl-L-carnitine treatment increases nerve growth factor levels and choline acetyltransferase activity in the central nervous system of aged rats. Exp Gerontol 1994 Jan-Feb;29(1):55-66.
  5. Garrett NE, Malcangio M, Dewhurst M, Tomlinson DR. alpha-Lipoic acid corrects neuropeptide deficits in diabetic rats via induction of trophic support. Neurosci Lett 1997 Feb 7;222(3):191-4.
  6. Emanuele E. NGF and romantic love. Arch Ital Biol 2011 Jun;149(2):265-8.