Palmitic Acid Is Androgen Agonist, Increases Androgen Synthesis, Decreases Cortisol

Palmitic acid has a bad reputation in mainstream medicine and the blogosphere. It is claimed to directly cause insulin resistance, obesity and even hypogonadism. Well, these studies found the exact opposite. The first one found that methyl-palmitate (MP) is an actual androgen receptor agonist. This is a very rare find since as the study explains, dietary androgenic substances are virtually unknown in the scientific literature. Notable, methyl-oleic acid (MO) was without effects on its own, but when combined with MP the combination increased T levels in addition to the androgenic effects of MP.
The second study shows that palmitic acid increased pregnenolone, DHEA in the adrenals, while at the same time decreasing cortisol synthesis. While the study did not find a direct effect of palmitic acid on activity of 17-20-lyase, I think it is very likely that such effect exists given the much bigger increase in androgen synthesis compared to using ACTH/forskolin alone. The activity of 17,20-lyase is the primary controller of androgen synthesis and more importantly for the conversion of pregnenolone into DHEA. Much to my chagrin, pregnenolone on its own is quite ineffective in raising androgen (or even DHEA) levels in humans and this is due largely to the declining activity of 17,20-lyase with age as well as the inhibitory effects of higher doses pregnenolone on this enzyme. If there is a way to boost 17,20-lyase activity then pregenolone can become an awesome prohormone and potentially remove the need for much of the male HRT administered by doctors today, as it would also largely avoid the estrogenic effects of using large doses of DHEA directly.
So, a cool experiment would be to take 100mg -200mg oral pregnenolone with a tablespoon of palmitic acid or even coconut oil. On my end, I will probably add palmitic acid as an ingredient in our supplement Gonadin to increase its direct androgenic effects.

Androgenic effect of honeybee drone milk in castrated rats: roles of methyl palmitate and methyl oleate. - PubMed - NCBI
"...NMR and MS measurements after the second fractionation revealed MP and MO in the last active fraction (II/E) of the raw DM. Although MO alone had no effect on androgen-sensitive organs, MP (similarly to raw DM) increased the weights of the androgen sensitive organs (except the prostate) and these effects were flutamide-sensitive. Palmitate is known to play a role in steroidogenesis: it is able to increase the DHEA level through its CYP17 activity (Bellanger et al., 2012). A fatty acid infusion has been reported to elevate human androgen production in both sexes (Mai et al., 2006, 2008). MP was recently proved to inhibit carrageenan-induced paw oedema by reducing the prostaglandin E2 level (Saeed et al., 2012), an effect which might indicate a steroidogenesis-inducing property. Since DHEA alone has a weak androgenic effect, the putative DHEA-elevating effect of MP may explain in part the response of androgen-sensitive organs. The androgenic dose (25 μg/kg) of MP alone did not alter the plasma testosterone level, but its combination with MO in high dose exhibited plasma testosterone-increasing effect, similarly to the action of raw DM. It is known that oleic acid has a weak 5-α- reductase inhibitory effect, preventing testosterone conversion to dihydrotestosterone, whereas the esterified analogues of oleic acid (like MO) are ineffective in this respect (Liu et al., 2009). As yet we have no explanation as to why the combination of MP and MO increases the plasma testosterone level in rat. Nevertheless, we have clearly shown that these two compounds have a major role in the main androgenic action of DM. Further studies are required to clarify the androgenic mechanisms of action of MO and MP."

Saturated fatty acid exposure induces androgen overproduction in bovine adrenal cells. - PubMed - NCBI
"...As expected, Table 1 shows that all steroid concentrations in the medium were significantly and markedly increased under ACTH stimulation, by 5–78-folds (Ps ≤ 0.001), as well as under fsk stimulation, by 6–63-folds (Ps < 0.005). Under conditions not stimulated with ACTH or fsk, palmitate exposure did not significantly change production of DHEA, androstenedione and cortisol. However, following stimulation by ACTH or fsk, palmitate increased pregnenolone production by about 20%, as compared to the absence of palmitate, but this was not statistically significant (P = 0.12 and 0.27, respectively). In presence of palmitate, cells significantly increased their production of the two other Δ5-steroids, 17OH-pregnenolone and DHEA, by 46% and 38% under ACTH stimulation (P = 0.02 and 0.05, respectively) and by about 70% under fsk stimulation (P = 0.01 and 0.007, respectively). Production of the Δ4-steroids was not affected by palmitate exposure, except for a significant reduction in androstenedione production by 32% under ACTH stimulation, as compared to ACTH-stimulated androstenedione production without palmitate (P = 0.02). This decrease was not observed however when androstenedione production was stimulated with fsk. Regarding glucocorticoids, 11-deoxycortisol production was significantly decreased by 25% when cells were exposed to palmitate, as compared to no exposure, both under ACTH (P = 0.05) and fsk (P = 0.02) stimulation. Similarly, cortisol levels in cell medium were significantly reduced by 25% following treatment with palmitate and stimulation with fsk, as compared to fsk alone (P = 0.003); but this decreased was less pronounced under ACTH stimulation (by 15%) and not statistically significant (P = 0.15)."

 

I have been taking a weekly dose of pregnenolone in the 300mg area recently, I will add coconut oil to the dose this week, and report back any interesting results. Also plan to try out gonadin with coconut oil as well.

 

What's wrong with the following study then?

Palmitic acid strongly boosts metastasis in mouse models of human oral cancer cells. Among all fatty acids, it has the strongest effect in boosting the metastatic potential of CD36+ metastasis-initiating cells.

Together, our results indicate that metastasis-initiating cells particularly rely on dietary lipids to promote metastasis.

http://www.nature.com/nature/journal/v541/n7635/full/nature20791.html

 

I was on coconut oil before using preg. I responded super well to preg when I started it, and I continued the use of coconut oil when I started preg as well with continued benefits that a lot of other PFS ppl didn't get. I responded super well to preg in an androgenic way (major libido boost), maybe that is the reason, but hard to tell since I don't really have an exact starting point. I cook with coconut oil and use 1 tbslpoon 3x daily of organic spectrum refined with meals.

 

Ah, so this is why most African males I see are so well built physically!

Palm oil is consumed quite a lot in some African countries and cultures.

 

The effects of palmitic acid were specific only for CD36+ cells.
"...In addition, exposure of cultured OSCC cells to palmitic acid, a dietary fatty acid recognized by CD36 (ref. 29), for 2 days also robustly increased the percentage of CD36+ cells (Extended Data Fig. 6e). Palmitic acid increased the size and frequency of lymph node metastases in a manner dependent on CD36, without affecting primary tumour growth."

I am not excluding the idea that increased fat load can be detrimental to cancer. In fact, once cancer develops, restriction of fat of ANY kind is probably wise. The study you posted also found that a simple HFD diet (not enriched with palmitic acid) also promoted metastasis and did so more than palmitic acid alone. Hence the benefit observed with niacin/niacinamide treatments. Ideally, cells should be burning sugar, not fat (except muscles at rest).

 

(sorry I'm french)

What I understand is androgen agonist is not exactly the same as androgen synthesis stimulator.

so(if I understand correctly) in the first study, it's methyl-palmitate the androgen agonist, does palmitic acid in its own a androgen agonist?
Does the body produce methyl-palmitate, I search on Internet but not find informations on this.

haidut: thank you for all the informations you give us.

 

Yes, MP was the androgen agonist but on its own it did not raise T levels. When combined with MO, it had all the androgenic effects AND raise T levels.
MP and MO are produced in the body but in small quantities. I think alcohol consumption raises their levels.

 

Interesting because a lot of people report a deeper voice after a night of drinking, a few feel great and refreshed .

 

Alcohol also is a great stimulator of 17,20-lyase and also lowers cortisol in the short run. So, a single night of drinking can bring good sexuality through raised androgens and less stress for some people. Obviously done chronically it does the opposite but I think there is a reason alcohol is so widely consumed - people feel good on it.

 

This study shows that lard thats high in palmitic and oleic acid was far better at raising testosterone than even coconut oil, despite its higher PUFA content.

Seems to support your info here nicely.

https://www.researchgate.net/public...nopeptidase_A_and_Blood_Pressure_in_Male_Rats

If humans aren't very good at making fats from sugar perhaps someone seeking to maximize androgens/testosterone would want to eat a fat with a good amount of palmitic and oleic acid, like cocoa fat or butter.
@haidut

 

Any idea why palm oil gives me gas, headaches, and black stool? Does it stimulate bile production? Is this possibly "liver cleansing" going on? Or simply viscosity irritating intestines (which doesn't explain black stool) as somebody has suggested?

Presumably topical use would have the same benefits and minimize these negatives?

 

Have you tried different brands?

 

I've not. The brand I have tried is Nutiva which I understand to be quite reputable (which doesn't prove anything). But let me add that caprylic acid does the same thing precisely. Coconut does it a little, but not nearly as severe.

 

Weird. Do you consume them with a meal? Or alone?

 

Alone.

 

Maybe try them or whichever with a meal. Will also help increase digestion and absorbtion of the rest of the food.

 

Agreed, as palmitic acid synthesis from sugar does not kick in for most people until they eat a few hundred grams of it. So, butter, cheese, milk, meat, cocoa fat, coconut oil etc are all good sources.

 

Saturated fats can cause some intestinal discomfort initially, especially the MCT products. It seems to dissipate with use. I would follow up on the black stool though. It may be a sign of upper GI bleeding due to ulcer or esophageal bleeding. You can do a test for H. pylori to easily confirm or rule out ulcers.

 

Sure. Just to be clear, it goes away without Palm oil/Caprylic acid. And I shouldn't have called it "black". Rather, I should have said "dark". Which is why I asked if they stimulate bile.