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A Possible Treatment For Erectile Dysfunction And Other Related Issues.

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#1 fishinghat


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Posted 17 February 2024 - 02:02 PM

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
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.
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.
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.
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.
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.
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.
Did you get experience genital numbness at all as part of your PSSD?
idk if the supplements helped or it passed on its own, but yes I did. and don’t now
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
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. 
Excellant summary article on PSSD/L-Citrulline
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...
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!!
I'm glad this is working for you. Did it improve genital numbness in anyway? I find this to be the biggest problem....
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.
Same problem here for me.
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.
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).

#2 fishinghat


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Posted 17 February 2024 - 02:06 PM

Other L-Citrulline health related uses.


Lipid Profile
1 week of citrulline consumption did not change other parameters, including plasma lipids, glucose, and NO3 (a metabolite of NO) 
We found no significant between-group differences in serum total cholesterol, HDL cholesterol, and TG concentrations 
 15 healthy male subjects (age: 58.3 ± 4.4 years) were given 5.6g/day of L-citrulline (n=8) or placebo (n=7) for 7 days.  No significant differences in blood pressure (BP) were found between the two groups.
 L-arginine or L-citrulline administration reversed the increase in serum AST and ALT activities, urea and all lipid profiles. These effects were associated with a concomitant increase in HDL-c and nitric oxide levels.
Non-significant differences were found between groups in term of albumin (p = 0.58), triglyceride (TG) (p = 0.68), high density lipoprotein (HDL-C) (p = 0.59), AST (p = 0.22), ALT (p = 0.75), and BUN (p = 0.40). (10 gram/day)
TG dropped 26.4%
LDL dropped 10.8%
HDL increased 6.5%
Arginase is overactive in psoriatic skin, leading to a relative increase in the consumption of arginine. We therefore hypothesize a relative decrease in NO synthase-derived NO production. NO donors may be effective topical treatments for psoriasis.
We will also discuss specific PAD isozymes (Protein Arginine Deiminase) that are associated with certain types of diseases, such as PAD1 is linked to psoriasis. Psoriasis is a type of dermatitis characterized by excessive proliferation and atypical epidermal differentiation which contribute to the flaky, dry patches of skin [19, 38]. The possible cause of the disease can be explained due to the fact that there is no citrullinated keratin K1 found in skin samples from patients with psoriasis [15, 18–19, 38]. The lack of citrullinated proteins causes excessive cornification and an inflammatory response [15, 18–19, 35, 38]. Psoriasis is the only disease linked to PAD1 dysregulation and it is unknown what triggers its decreased enzymatic activity [15, 18, 35, 38]. 
As mentioned in Section 3.5, PAD4 is involved in a unique form of cell death, ‘NETosis’. Released NETs actively trap bacteria and other pathogens that prompt this type of immune response. This immune response is a common defense mechanism against foreign microbes. The effects of NET dysregulation play a role in a number of other autoimmune diseases, including psoriasis [92], systemic lupus erythematosus (SLE) [93], and RA as previously discussed. Interestingly, pro-inflammatory IL-17 is released during NET formation in psoriasis, SLE, and RA, indicating that this aberrant immune response triggers an inflammatory response [89, 92, 94].
Peptidylarginine deiminase (PAD, EC enzyme catalyzes the conversion of arginine residues to citrulline residues in the presence of calcium ion, which is an elaborate post-translational modification on the target protein. Recently, five isoforms have been identified in mammals. Among them, three isoforms (type I, II, III) are expressed in the human epidermis, and involved in several skin physiological and pathological processes. In the past few years, several researches concerning the transcriptional regulation of three human PADI type genes (PADI1, PADI2 and PADI3) in the epidermis have been carried out. In this review, we describe an overview of the current outcomes about these studies with their significance. It is anticipated that these investigations will provide novel therapeutic and prophylactic targets for future approaches to the treatment or prevention of severe psoriasis and bullous congenital ichthyosiform erythroderma.
 The metabolites present on L skin-in particular, choline, and citrulline-showed greater dynamics, corresponding to the resolution of psoriasis than the metabolites present in NL skin or blood. Choline levels in L skin and blood correlated positively, while citrulline correlated negatively with the severity of individual psoriasis plaques and general disease severity, respectively.
 It has been suggested that homocysteine leads to endothelial dysfunction by causing an accumulation of asymmetrical dimethyl arginine (ADMA), a potent endogenous nitric oxide (NO) synthase inhibitor of the L-arginine-NO pathway. However, limited data is available regarding the psoriasis and ADMA relationship. In this study, we aimed to investigate the serum levels of homocysteine, ADMA and other metabolites from the L-arginine-NO pathway in psoriasis patients. Forty-two patients with chronic plaque psoriasis and 48 controls were enrolled in the study. Serum homocysteine, ADMA, L-monomethyl-L-arginine (L-NMMA), symmetric dimethylarginine (SDMA) and L-arginine levels, and L-arginine/ADMA ratios of psoriasis patients and the control group were measured. The severity of psoriasis was assessed by the psoriasis area and severity index (PASI). The mean ADMA and homocysteine values were significantly higher, and citrulline and L-arginine/ADMA values were significantly lower in psoriasis patients compared to control subjects. This study suggests that the L-arginine-NO pathway metabolites, especially ADMA, may play an important role in the pathogenesis of psoriasis. Additionally, serum ADMA levels of psoriasis patients may be an indicator of the disease severity.
Here, we show reduced levels of peptidylarginine deiminase 1, an enzyme that converts peptidylarginine into citrulline in lesional psoriatic skin.
Quantitative Analysis of Free Amino Acids and Urea Derived from Isolated Corneocytes of Healthy Young, Healthy Aged, and Diseased Skin
Unlike the other FAAs and urea, citrulline was found at a higher level in the healthy young group than in the disease groups.
Citrulline-containing proteins, mainly originating from keratin K1 and formed by enzymatic deimination of arginine residues, have been identified in the cornified layers of human epidermis. We analyzed the localization and nature of the deiminated proteins in psoriatic epidermis. Immunostaining based on chemical modification of citrulline residues showed that the normal and psoriatic uninvolved epidermis contained deiminated proteins diffusely in the cornified cell layer, whereas the involved epidermis had no detectable or markedly reduced levels of deiminated proteins.

#3 invalidusername


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Posted 20 February 2024 - 06:46 PM

Lots of useful information here Hat - and something that I know is close to you so you naturally have a passion for finding a means around PSSD.


Obviously with more and more drugs coming out, it is natural that people are going to find these things as an issue. Great to have it posted here and in due course, in the eBook.


Keep up the good work!



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