A possible treatment for erectile dysfunction from PSSD (post ssri sexual dysfunction), antidepressant sexual dysfunction, as well as libido and/or vaginal dryness.
It has long been known that nitric oxide is critical for sexual function and libido. Nitic oxide increases blood flow to most organs of the body. Our body produces nitric oxide by the processing of the amino acid L-Arginine. Research into the taking of L-Arginine supplements has shown little benefits though. Research in the recent past has shown that L-Arginine is largely destroyed (approximately 90%) when taken as a supplement and results are minimal at best. Research has also shown that most of the L-Arginine found in the human body comes from converting L-Citrulline (another amino acid) into L-Arginine. Unluckily as we age our body does not absorb amino acids or convert them to usable compounds very efficiently.
In recent years erectile dysfunction and PSSD websites have had many posts about using L-Citrulline for these types of conditions but results have varied considerably. It should be noted that the people posting on these cites didn't just get sexual dysfunction from antidepressants, withdrawals or old age. Some were from nerve damage, surgeries... Also there wa no standard approach to the dose of L-Citrulline.
---------------------------------------------------------------------------------------------------------------
After reviewing over 50 posts on several websites I developed a plan for the use of L-Citulline for sexual dysfunction in myself. The following is a summary of my approach.
(Please note that I am NOT a doctor and this has just been the approach I and a few others have used to address our issues.)
1) Due to some complaints from people who posted that it can cause bloating I took a tip from some to start with 750 mg once a day and then every 3rd day increase by 750 mg until a dose of 6000 mg is taken daily for men and/or 4000 to 5000 mg daily for women.
2) Those doses should be 1500 mg at 4 times a day for men and 1500 mg 3 times a day for women. Each 1500 mg dose should be seperated by at least 2 hours before taking the next dose. If all 4000 to 6000 mg is taken at the same time than most of the dose over 1500 mg is passed out in the urine.
3) It takes L-Citulline 2 to 4 weeks to take full effect.
Note these doses are about 50% to 100% higher when compared to research using L-Citrulline for erectile dysfunction in (primarily) older men.
----------------------------------------------------------------------------------------------------------------
Effects of this protocol in specific cases known to me.
Fishinghat - Written 1/26/2023 (Updated 2/10/24)- I went through Cymbalta withdrawal in early 2013 due to it causing total loss of testosterone production. Shortly after I stopped Cymbalta use and I had 4 days of hypersexuality and then went into full PSSD. I had not had a single erection in nearly 11 years. In addition I am very old and that probably makes issues even worse. Due to the failure in testosterone production I went on topical testosterone in mid-2013 and have maintained proper testosterone levels since but that did not have any effect on my erectile function or my penile anesthesia. In the last few years I had developed urinary urgency and some light incontinance. I started on this L-Citrulline protocol the day before Christmas 2023. I have been on 6000 mg of L-Citrulline since Jan 19th. I am now experiencing no penile anesthesia; erections that are 20% - 80% of normal and can last 1 - 3 minutes. Not bad for a person who hasn't had an erection in over 10 years. My urinary urgency and some of the light incontinance has totally disappeared. My penile anesthesia is gone as well. It will be interesting to see if these characteristics continue. The L-Citrulline has all but cured my psoriasis that I have had for 45 years.
2/17/24 update - Things continue doing well with erections continuing to improve slowly. I have also tried 5 grams L-citrulline in a one time dose about 1 to 2 hours before intercourse with an associated slight improvement in function and endurance. I am now at over 4 weeks on full dose of L-Citrulline so I don't expect much more improvement.
JJ - Elderly female - Written 1/24/2023 (updated 2/10/24) More than 10 years post-menopause with Postmenopausal Syndrome. This includes significant urinary incontinance and urgency which has been treated with pharmaceuticals for the last 8 years. Since on L-citrulline she has had no more vaginal dryness. Currently on 4,500 mg L-Citruline as of this date. Libido is very good. Urinary incontinance and urgency are 50% better and no vaginal dryness at all. She has been on full dose just 1 week.
JJ is not a member of this forum but my thanks to her for allowing me to share this information with all of you. I have guaranteed her anonymity.
---------------------------------------------------------------------------------------------------------------
Some of the related research
(2011)
Single-blind study, men with mild ED (erection hardness score of 3) received a placebo for 1 month and L-citrulline, 1.5 g/d, for another month. A total of 24 patients, mean age 56.5 ± 9.8 years, were entered and concluded the study without adverse events. The improvement in the erection hardness score from 3 (mild ED) to 4 (normal erectile function) occurred in 2 (8.3%) of the 24 men when taking placebo and 12 (50%) of the 24 men when taking L-citrulline (P < .01).
Note - This is just one of many research articles on the use of L-Citrulline for Erectile Dysfunction in older men.
(2017)
Our study shows that a significant proportion of erectile dysfunction patients have low l-Arg or l-Cit level and that this condition is more frequent in patients with arteriogenic etiology. Low levels of these nitric oxide synthase substrates might increase the erectile dysfunction risk by reducing the concentration of nitric oxide.
Other research on L-Citrulline includes urinary incontenance, raising good cholesterol and lower triglycerides (a fat type molecule that can collect in arteries and cause cardiac issues) as well as psoriasis. The research data on each of these is given below.
L-arginine
This amino acid helps create nitric oxide. Nitric oxide plays an important role in the health of the lower urinary tract. There are not a lot of studies that look at L-arginine in overactive bladder.
One study found that the supplement Edicare, which contains 115 milligrams of L-arginine, is helpful for OAB in older adults.
Avoid L-arginine if you have:
an allergy to arginine
a bleeding disorder or are taking blood thinning medications
diabetes or hypoglycemia
hyperkalemia, or high levels of potassium
an immune system disorder
It should be noted that Paxil (Paroxetine) inhibits niutric oxide production.
See - https://pubmed.ncbi....ih.gov/8993087/ and
------------------------------------------------------------------------------------------------
Libido In Women
The NO-cGMP pathway plays a key role in the male and female genital sexual arousal response. Nitric oxide synthase (NOS) utilizes L-arginine and oxygen as substrates to produce nitric oxide (NO) and citrulline. We present data to suggest that arginase may regulate NO production by competing for endogenous pools of L-arginine. In this fashion, arginase is an indirect regulator of penile and vaginal blood flow.
Nitric oxide used to treat female sexual arousal disorder.
Vasoactive intestinal peptide and nitric oxide may be responsible for the increase in vaginal blood flow during sexual arousal.
During arousal, nitric oxide is the main neurotransmitter for smooth muscle relaxation in both male and female erectile tissue.
Estrogens control vaginal blood flow during female sexual arousal mostly through nitric oxide (NO).
NOS and PDE5 in the vagina may play important roles in the pathophysiology of FSD.
Note many more references exist. Please also note that the primary route for generating nitric oxide is the ingestion of L-Citrilline which is converted to L-arginine in the body which can then liberate nitric oxide and increase blood flow and moisture to the penis and vagina.
------------------------------------------------------------------------------------------------------------------
PSSD
(2022)
Herein we report on a young man affected by PSSD who regained sexual functioning after 3-month treatment with EDOVIS, a dietary supplement containing L-citrulline and other commonly used aphrodisiacs.
Forums
pssdthrowaway3
Tongkat Ali, l-citrulline, and vitamin D have worked miracles on me.
I started all of these supplements at the same time and I think I may be hornier than my pre PSSD state. I’m genuinely blown away and it happened almost overnight. 1g tongkat 6g citrulline and I take it EVERY SINGLE DAY BABY
For context, I had PSSD for 2 years and it’s healed basically over the last couple of days. I’ve tried all kinds of supplements like cordyceps, maca, shrooms, acid, coffee, and many many more with no benefit.
nainsra
Did you get experience genital numbness at all as part of your PSSD?
pssdthrowaway3
idk if the supplements helped or it passed on its own, but yes I did. and don’t now
-----------------------------------------------------------------------------------------------------------------
f30bim
Has anyone tried L-citrulline ?
Just curious about how it would work for me because all research articles on the drug are tested on men with erectile dysfunction
Pokebongo
I’ve taken a ton of it. As others have said it’s great for erections and that’s about it. I don’t know what to say about curing the numbness. I’m starting to think it is indeed permanent.
-----------------------------------------------------------------------------------------------------------------
Bubzoluck
Excellant summary article on PSSD/L-Citrulline
FoxPssd
it is a nice theoretical summary, but citruline has been trialed quite a bit, with mediocre results. From personal experience; it gives me brainfog and doesnt do much on libido. Maybe others had better results...
---------------------------------------------------------------------------------------------------------------
FarTrick
l-citrulline has helped IMMENSLEY and consistently so! 
I've been taking l-citrulline daily for about 2 months and I now have morning wood, spontaneous erections, and FULL erections! I get full erections when thinking about my crush, when I see an attractive woman etc etc and these erections stay for a while (like I have to "fight" mentally for them to go away, which is how it was before ssris)
I take NOW brand of l-citrulline (750 mg) and I take 2 pills in the morning and 2 at night!! For about the first month I only took two a day, but wanted to see what would happen if I took a lil more. been taking 4 a day for a month now and I feel great!!! Hope this helps you guys!!
Expensive-Director87
I'm glad this is working for you. Did it improve genital numbness in anyway? I find this to be the biggest problem....
FarTrick
Therein lies the rub-- I still have very little sensation as far as I can tell, however this is by far the biggest and most consistent change for me, so I'm taking it as a win. If I can have firm and lasting erections I figure that'll be enough to satisfy any partner I have down the road. I know this isn't easy, but I have pretty much made my peace that sensation is gonna be gone for as long as I'm around. I will msg u back if that ends up changing somehow.
ImaginationCommon930
Same problem here for me.
----------------------------------------------------------------------------------------------------------------
Testosterone
12 grams L-Citrulline per day increased testosterone in rams.
The bioavailable testosterone concentrations were decreased in the castrated and castrated + L-citrulline groups compared with the control group at 4 weeks after surgery.
----------------------------------------------------------------------------------------------------------------
Estrogen
No medical research was located on the effect of L-Citrulline on estrogen levels.
---------------------------------------------------------------------------------------------------------------
Vaginal Dryness
Prevention of vaginal dryness in perimenopausal women. Supplementation with Lady Prelox
Standardized supplement (Lady Prelox®, Horphag Research) - including Pycnogenol®, l-arginine, L-citrulline and rose hip extract - to improve signs and symptoms associated with vaginal dryness in pre and post-menopausal healthy women. No safety problems were observed with the supplement that was well tolerated. Among pre-menopausal women, results of the female sexual function index (FSFI) were significantly improved with the supplement in comparison with the control subjects' group (P<0.05). The results of the FSFI questionnaire for post-menopausal women indicated a significant improvement at 8 weeks with Lady Prelox® (P<0.05) in comparison with controls. Preclinical items (vaginal dryness, pain/discomfort during intercourse, mucus, minimal infections, presence of candida and oxidative stress) were significantly improved (P<0.05) with Lady Prelox®) in comparison to minimal changes with the SM group. These measurements included all women. The effects of the supplementation with Lady Prelox® on vaginal dryness were significant.
------------------------------------------------------------------------------------------------------------------
Half-life of L-Citruline
1 hour/infants and children
Plasma half-life and exposure of citrulline also increased dose-dependently and the Tmax and Cmax were determined for both citrulline (Tmax = 0.72±0.08 h, Cmax = 2756±70 μmol/l) and arginine (Tmax = 1.67±0.05 h, Cmax = 280±1043 μmol/l)
Rmax 1.6 hrs for 1.5 grams L-citrulline twice a day.
Both Arg and Cit are effective at increasing plasma Arg. Cit is approximately twice as potent, which is most likely due to a lower first-pass metabolism. The current data suggest that oral Arg supplementation can lower BP by 5.39/2.66 mmHg, which is an effect that is comparable with diet changes and exercise implementation. The antihypertensive properties of Cit are more questionable, but are likely in the range of 4.1/2.08 to 7.54/3.77 mmHg.
The half-life appears to be dose-dependent, with the most relevant data being a half-life of 76+/-9min following oral intake of 6g Arginine
Table 1 Pharmacokinetic parameters of plasma citrulline after citrulline loads administered to healthy volunteers*
tmax, Time of maximum concentration; Cmax, maximum concentration; AUC, area under the curve, Vd, distribution volume; ln, natural log-transformed.
a,b,c,d Values within a column with unlike superscript letters are significantly different (P < 0·05).
* For details of the parameters explored, see the Statistical analysis section. ANOVA and Tukey's honestly significant differences test were performed on tmax, ln(ΔCmax), t1/2, ln(ΔAUC0 − ∞), clearance and Vd.
Table 2 Pharmacokinetic parameters of plasma arginine after citrulline loads administered to healthy volunteers*
tmax, Time of maximum concentration; Cmax, maximum concentration; AUC, area under the curve; ln, natural log-transformed.
a,b,c,d Values within a column with unlike superscript letters are significantly different (P < 0·05).
* For details of the parameters explored, see the Statistical analysis section. ANOVA and Tukey's honestly significant differences test were performed on tmax, ln(ΔCmax) and ln(ΔAUC0–8).
-------------------------------------------------------------------------------------------------------------------
