PUFA And MUFA Are Strong Inhibitors Of 5-AR, Saturated Fatty Acids Are Not

haidut

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I have posted quite a few studies showing the effects of various fatty acids on estrogen, androgen and glucocorticoid synthesis. This study shows that both PUFA and MUFA are strong inhbitors of 5-AR, with PUFA being the more potent inhibitors and inhibition potency being strongly dependent on the degree of unsaturation of the fatty acid. As you can see from the attached screenshot, DHA, arachidonic, GLA, and linoleic acids were the most potent inhibitors. Saturated fatty acids were completely inactive as inhibitors of 5-AR. Methylated unsaturated acids like methyl oleate (component of Gonadin) were also inactive. Some prostaglandins were inhibitors confirming again the link between inflammation and lower androgen levels. Phosphatidylcholine and vitamin A derivatives were actually stimulating.

Inhibition of steroid 5 alpha-reductase by specific aliphatic unsaturated fatty acids. - PubMed - NCBI

"...We therefore tested various lipids for their ability to affect binding of [3H]4-MA to rat liver microsomes. Table 1 shows that only certain unsaturated fatty acids are inhibitory. Among the lipids we have tested, inhibitory fatty acids have 14-22 carbon chains and one to six double bonds. Presence of a double bond was required for inhibitory activity; saturated fatty acids were totally inactive. Only compounds with double bonds in the cis configuration were active at low concentrations (< 10 JM), whereas the trans isomers were inactive even at high concentrations (> 0.2 mM). The difference in the effects of cis and trans isomers of fatty acids is obvious when the following sets of fatty acids are compared: oleic acid (C18.l cis9) versus elaidic acid (C18: 1 trans-9), and linoleic acid (C18:2 cis-9,12) versus linolelaidic acid (C18:2, trans-9,12). The number and the position of the double bonds also affected the potency. For example, the inhibitory potencies of the C18 fatty acids were, in decreasing order: y-linolenic acid (cis-6,9, 12) > octadecatetraenoic acid (cis- 6,9,12,15) > a-linolenic acid (cis-9,12,15) > linoleic acid (cis- 9,12) > oleic acid (cis-9) > petroselinic acid (cis-6). Erucidic acid (C22: 1,cis-13) was inactive, whereas cis-4,7,10,13,16,19-docosahexaenoic acid was a potent inhibitor. Undecylenic acid (C11:110) and nervonic acid (C24:1 cis-15) were also inactive. A free carboxyl group is important, since the methyl ester and alcohol analogues of these inhibitory unsaturated fatty acids were either inactive or only slightly active. Prostaglandin E2, F2, and I2 were also not active, whereas the A1, A2, B1,,2 D2, E1 and F1 forms were somewhat active at 0.2 mm. Carotenes, retinals and retinoic acid were also inactive. Phosphatidylcholine, phosphatidylethanolamine, 3-diolein, retinol, 13-cis-retinoic acid, and 13-cisretinol were slightly stimulatory."
 

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Dante

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What about mead acid ? 3 -cis double bonds with a carboxyl group ?
 

tankasnowgod

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Look at that..... Trans Fats were also inactive! I dug a little bit into the idea that Trans Fats are bad for the heart........ seems like all the evidence rests on HDL/LDL/Triglyceride changes that rest on the Lipid Hypothesis, or observational studies, where Trans Fats could just as easily be a surrogate marker for high PUFA vegetable oils.

So, Mitolipin not only works for saturating fat stores if applied topically, but should stimulate 5-AR as well?
 

The_xXx

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eggs have archadonic acid so why peat recommends us to eat every day 2 of them ?
 
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haidut

haidut

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What about mead acid ? 3 -cis double bonds with a carboxyl group ?

Good point, not much data on it out there. But given that it is a biomarker of EFA deficiency and hyperthyroidism, I doubt it is an 5-AR inhibitor.
 
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haidut

haidut

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Look at that..... Trans Fats were also inactive! I dug a little bit into the idea that Trans Fats are bad for the heart........ seems like all the evidence rests on HDL/LDL/Triglyceride changes that rest on the Lipid Hypothesis, or observational studies, where Trans Fats could just as easily be a surrogate marker for high PUFA vegetable oils.

So, Mitolipin not only works for saturating fat stores if applied topically, but should stimulate 5-AR as well?

Some trans fats have been known to be good for CVD and insulin sensitivity for a long time.
Dairy fat may help not harm

Yes, MitoLipin and DeFibron should stimulate 5-AR as well as help change fatty acid profile in the cell.
 
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tca300

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I wonder why other studies show lauric acid, palmitic, etc lowering 5-AR?
Confusing.
 
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haidut

haidut

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I wonder why other studies show lauric acid, palmitic, etc lowering 5-AR?
Confusing.

Can you share those please? I have not seen any studies on palmitic acid lowering 5-AR.
 
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tca300

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Anti-androgenic activity of fatty acids. - PubMed - NCBI
Mentions saturated fats with 12-16 carbon length ( palmitic has 16 ) were inhibitory. I cant access all the details. Im not trying to disagree, I tend to think the saturated fats are pro DHT based on how they make me feel, but once again, studies confuse me. With all the studies showing its pro or at least neutral in regards to 5AR, there is likely something fishy or incorrect in regards to this one.
 
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RMJ

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i just started to eat a lot of egg yolks to see if it improves libido

but reading this makes me think about stoping it
 
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haidut

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Actually, the studies you provided kind of confirm the one I posted pretty well. See attached screenshots and excerpts below. SCFA like lauric, and butyric (and MCFA like myristic) are inhibitory but still much less so than unsaturated ones like oleic and linoleic. Unsaturation was once again correlated with inhibitory potency. I guess palmitic and stearic acids would be the safest. Since methyl esters were inactive, the methyl myristate in our DeFibron should not be an issue and should not affect the androgenic features of methyl palmitate.

"...5a-Reductase Inhibitory Activity. Fig. 1 shows that only certain saturated fatty acids have inhibitory activity. Among the saturated fatty acids, the inhibitory acids (more than 50% inhibition at 1.3 mm) have C12 – C16 chains. The relative inhibitory potencies for the 5a-reductase of saturated fatty acids are, in decreasing order, C12>C14>C15> C16>C18 . This result suggested that the 5a-reductase inhibitory activity of saturated fatty acids depends on the hydrocarbon-chain length. This result was similar to those reported by Niederprm et al. [14]. When C18 fatty acids were investigated, only the unsaturated compounds showed 5a-reductase inhibitory activity of greater than 50% inhibition at the concentration of 1.3 mm (Figs. 1 and 2, and Table). The presence of a C=C bond enhanced the inhibitory activity (Figs. 1 and 2, and Table). The number and position of the C=C bonds also affected the potency. For example, the C18 fatty acids can be listed in decreasing order of their inhibitory potencies as follows: a-linolenic acid, linoleic acid, oleic acid, and stearic acid. Compared with the active fatty acids, methyl ester and alcohol analogues showed a lower level of 5a-reductase inhibitory activity. The free COOH group is important, since the methyl ester and alcohol analogues of these inhibitory unsaturated fatty acids were either inactive or only slightly active."

"...The curves of inhibition for the main free fatty acids present in the extract are depicted in Fig. 1 and the results given in Table 1. We can easily see from the graphs, that there are striking differences depending on the length of the carbon chain and its saturation state. Lauric acid (short saturated C12 chain) was a good inhibitor of both 5R1 and 5R2. Myristic acid (saturated, C14 chain) strongly inhibited 5R2 (inhibition of 5R1 has not been measured). Palmitic (saturated, C16 chain) and stearic (saturated, C18 chain) acids were inactive on both isoforms (see Table 1). With a C18 unsaturated chain (oleic (C18 9) and linoleic (C18 9,12)), a selective inhibition appeared. In opposition to the inactive saturated chain of stearic acid, the two unsaturated chain fatty acids were good inhibitors of 5R1 only. In the esterified fatty acids assayed, there is no inhibition at all (see Table 1). Other constituents, present in minute quantities in the extract, are also inactive as illustrated for some of them in Fig. 2. The lack of efficacy of -sitosterol may be emphasised. It can thus be concluded that, to achieve inhibition of 5R1, oleic acid, representing one-third of the extract, is sufficient but that inhibition of total 5-reductase activity (5R1 and 5R2) can only be obtained when short chain free fatty acids (lauric and myristic acids) are present."
 

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haidut

haidut

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Anti-androgenic activity of fatty acids. - PubMed - NCBI
Mentions saturated fats with 12-16 carbon length ( palmitic has 16 ) were inhibitory. I cant access all the details. Im not trying to disagree, I tend to think the saturated fats are pro DHT based on how they make me feel, but once again, studies confuse me. With all the studies showing its pro or at least neutral in regards to 5AR, there is likely something fishy or incorrect in regards to this one.

See my response above and the screenshots. Unsaturated FFA were still the most inhibitory. Of the SFA, the shorter the chain the more inhibitory they are, so avoiding SCFA or combing them with androgenic and non-inhibiting ones like palmitic and stearic would be key.
 

Wagner83

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In this light coconut oil does not sound very good theoretically, unless used in very small doses.
 
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haidut

haidut

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In this light coconut oil does not sound very good theoretically, unless used in very small doses.

Possibly yes, but it has palmitic acid which may balance the effects of the inhibiting lauric and myristic. Are there any in vivo studis with FFA combinations as found in coconut oil or butter?
 

Wagner83

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Possibly yes, but it has palmitic acid which may balance the effects of the inhibiting lauric and myristic. Are there any in vivo studis with FFA combinations as found in coconut oil or butter?
I only found those:
Similar effects of diets rich in stearic acid or trans-fatty acids on platelet function and endothelial prostacyclin production in humans. - PubMed - NCBI
The effects of stearic acid (C18:0) and trans-fatty acids (trans-FAs) on measures of platelet function and prostacyclin (PGI2) production are poorly understood in humans. In this controlled dietary study, platelet function and endothelial PGI2 production were studied in healthy humans after they consumed diets rich in C18:0 or trans-FAs.
...
Effects of dietary saturated, monounsaturated, and n-3 fatty acids on blood pressure in healthy subjects. - PubMed - NCBI
CONCLUSIONS:
Changing the proportions of dietary fat by decreasing SFAs and increasing MUFAs decreased diastolic BP. Interestingly, the beneficial effect on BP induced by fat quality was negated by the consumption of a high total fat intake. The addition of n-3 fatty acids to the diet had no significant effect on BP.
Comparative effects of saturated and unsaturated lipids on hepatic lipogenesis and cholesterogenesis in vivo in the meal-fed rat. - PubMed - NCBI
These data suggest the following: a) fatty acid synthesis responds selectively to 18:0, 18:1, and 18:2; b) the inhibition of fatty acid synthesis by unsaturated fatty acids is time dependent; c) the rate of fatty acid synthesis is inversely proportional to the concentration of unsaturated dietary fat; d) prolonged feeding with a completely saturated diet will increase fecal fat excretion and hepatic cholesterol synthesis; and e) the regulation of fatty acid synthesis by dietary lipid is independent of the regulation of cholesterol synthesis.
I wonder if this increase in cholesterol synthesis is relevant for steroids/bile acids:
The effect of replacing dietary saturated fat with polyunsaturated or monounsaturated fat on plasma lipids in free-living young adults. - PubMed - NCBI
Replacing saturated fat with n-6 polyunsaturated fat (trial I) lowered plasma total cholesterol by 19% [from 4.87 (0.88) to 3.94 (0.92) mmol/l, mean (s.d.)], low density lipoprotein cholesterol by 22% [from 2.87 (0.75) to 2.24 (0.67) mmol/l], and high density lipoprotein cholesterol by 14% [from 1.39 (0.36) to 1.19 (0.34) mmol/l], whereas replacing saturated fat with monounsaturated fat (trial II) decreased total cholesterol by 12%, low density lipoprotein cholesterol by 15%, and high density lipoprotein cholesterol by 4%, respectively.


Comparison of the effects of diets rich in stearic acid versus myristic acid and lauric acid on platelet fatty acids and excretion of thromboxane A... - PubMed - NCBI
The present study compared the effects of diets rich in stearic acid (C18:0) versus one high in lauric and myristic acid (C12:0, C14:0) on platelet phospholipid fatty acid levels and concentrations of urinary thromboxane B2 (TXB2) and 6-keto-PGF1 alpha, which are stable metabolites of thromboxane A2 (TXA2) and PGI2 and indicators of cardiovascular hemostasis. A diet high in dairy butter (B) was the source of C12:0 and C14:0; C18:0 was provided by diets high in cocoa butter (CB), milk chocolate (CHOC) or CB+B in a 4:1 ratio (MIX). A randomized, crossover double-blind experimental design was used. Experimental subjects (n = 15) consumed each diet for 26 days, with a 1-month washout period between each experimental period.
Influence of stearic acid on cholesterol metabolism relative to other long-chain fatty acids. - PubMed - NCBI
Stearic acid is a long-chain saturated fatty acid. However, in contrast with other saturated fatty acids, stearic acid apparently does not raise serum cholesterol concentrations. Studies carried out three decades ago provided strong suggestive evidence that this was the case. More recent investigations that specifically compared stearic acid with other fatty acids in human studies have confirmed that stearic acid is not hypercholesterolemic. Stearic acid was shown not to raise low-density-lipoprotein cholesterol relative to oleic acid, which is known to be neutral in its effects on cholesterol concentrations. In contrast, palmitic acid, another long-chain saturated fatty acid, definitely raises cholesterol concentrations. For this reason, fats rich in stearic acid might be used in place of those high in palmitic acid in cholesterol-lowering diets.
The effect of short-term diets rich in fish, red meat, or white meat on thromboxane and prostacyclin synthesis in humans. - PubMed - NCBI
These results indicate that short-term diets which double the usual 20:4n-6 intake using white meat (175-330 g/d) or red meat (275-530 g/d) are not associated with an increased TXA2 production, but this does not rule out the adverse effects of 20:4n-6 at higher levels in the diet, or for more prolonged periods. Short-term diets containing fish (100-200 g/d with 90-210 mg/d 20:4n-6 and approximately 650-1000 mg/d 20:5n-3) led to significant increases in platelet 20:5n-3 levels and a decrease in the ex vivo and systemic TXA2 production.

Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU Study. - PubMed - NCBI
METHODS:
The KANWU study included 162 healthy subjects chosen at random to receive a controlled, isoenergetic diet for 3 months containing either a high proportion of saturated (SAFA diet) or monounsaturated (MUFA diet) fatty acids. Within each group there was a second assignment at random to supplements with fish oil (3.6 g n-3 fatty acids/d) or placebo.

RESULTS: Insulin sensitivity was significantly impaired on the saturated fatty acid diet (-10%, p = 0.03) but did not change on the monounsaturated fatty acid diet (+2%, NS) (p = 0.05 for difference between diets).

CONCLUSIONS/INTERPRETATION:
A change of the proportions of dietary fatty acids, decreasing saturated fatty acid and increasing monounsaturated fatty acid, improves insulin sensitivity but has no effect on insulin secretion. A beneficial impact of the fat quality on insulin sensitivity is not seen in individuals with a high fat intake (> 37E%).

Also:
Fatty acid composition of skeletal muscle reflects dietary fat composition in humans. - PubMed - NCBI
CONCLUSION:
The fatty acid composition of skeletal muscle lipids reflects the fatty acid composition of the diet in healthy men and women.
 

jaywills

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So where do we go from here regarding fats particularly for androgen optimisation 15-20% of Sat fat based sources?
 

Drareg

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Does Oleyl alcohol have enhancing effects? Is the chart implying this?
What's going on with Oleic acid then,is it converted into oleyl alcohol at any point?

This must be why Peat is recommending hydrogenated fats,people will think we have lost the plot on here,"peatarians" eating bags of sugar and hydrogenated fats,their so dogmatic etc
 

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