Soy Protein Isolate Reduces DHT in Healthy Young Men

Drinking soy milk shakes might reduce DHT in men. (Photo by lists&diagrams)

Last month, I wrote about a paper that suggested soy isoflavones reduce DHT and increase testosterone. I also promised to write blog posts about similar studies to get a better understanding of how soy affects androgen levels.

In the second study we'll be looking at, 35 men were given soy protein isolate or milk protein isolate for 2 months to see how it affected their reproductive hormone levels (link). There were two versions of the soy protein diet: the low-isoflavone and the high-isoflavone diet. Each participant was put on each of the three diets with a 28-day washout period in between them.

Composition of the diets

The low-isoflavone soy protein isolate contained 0.02 mg isoflavones/kg body weight, while the high-isoflavone isolate contained 0.72 mg/kg body weight. Mean soy isoflavone intakes were 1.64 mg and 61.7 mg, respectively, with the most abundant isoflavones being genistein and daidzein. The milk protein isolate contained no isoflavones.

A third of the participants were categorized as equol excretors (meaning their bodies were able to produce equol from soy isoflavones), which seems to be consistent with other studies. Especially from a hair loss perspective, equol shows great promise, but it's currently unclear whether it's possible to affect one's ability to produce equol.

Soy protein isolate and testosterone

Halfway through the experiment, testosterone levels were slightly lower in the low-isoflavone diet (19.8 nmol/L) than the high-isoflavone diet (22.0 nmol/L) and the milk protein diet (22.1 nmol/L). At the end of the experiment, there was no statistically significant difference between testosterone levels. Levels of free testosterone were similar during all three diets.

Soy protein isolate and DHT

Serum dihydrotestosterone (DHT) and was decreased by the low-isoflavone diet (1952 pmol/L) and the high-isoflavone diet (1962 pmol/L) compared to the milk protein diet (2155 pmol/L) at the end of the experiment. The ratio of DHT to testosterone was also decreased.

Soy protein isolate and other effects

At the end of the study, serum estradiol and estrone were increased by the low-isoflavone diet compared with the milk protein diet. Levels of SHBG, gonadotropins, and 3-alpha-AG (a marker of 5-alpha-reductase activity), did not vary significantly between the diets. DHEA-S was increased by the low-isoflavone diet, but DHEA levels were not significantly different.

Conclusion

Serum DHT was significantly reduced following the consumption of both a low-isoflavone and high-isoflavone soy protein isolate compared to a milk protein isolate. The reductions were 9.4% and 15%, respectively. The DHT/testosterone ratio was also decreased by 9.0% and 14%, respectively.

The reduction in the DHT/testosterone ratio suggests an inhibition of 5-alpha-reductase. However, 3-alpha-AG, a marker of 5-alpha-reductase activity, was not significantly affected. Levels of sex hormone-binding globulin (SHBG) were also not significantly different between the diets.

For more information on hair growth, see these posts:

Tea Tree Oil vs. Korean Red Ginseng – Hair Growth Battle Conclusion
North African Plant Extract (Erica multiflora) Increases Hair Growth
2% Nizoral Shampoo Increases Hair Growth More than 2% Minoxidil
Lygodium japonicum Promotes Hair Growth by Inhibiting Testosterone to DHT Conversion

Intermittent Fasting: Switching from Alternate-Day Fasting to Condensed Eating Window

Thankfully, coffee has zero calories. (Photo by Erik)

Time for another update on my intermittent fasting experiment, which has been running for 10 months now. As you probably know, intermittent fasting means alternating periods of eating with periods of fasting. The length of these periods varies depending on the type of intermittent fasting one does.

So far, I've been doing the 24/24 hour cycle, meaning that I eat for 24 hours and then fast for 24 hours. This is known also as alternate-day fasting (ADF) or every other day fasting (EOD). It has worked very well for me: the fasting periods are short enough for the hunger to be very bearable but long enough to (hopefully) see some long-term benefits such as improved insulin sensitivity and reduced mitochondrial damage. If you want to read more about what intermittent fasting is like in practice, I've written blog posts on my typical day and my typical high-fat, low-carb meal.

Starting yesterday, I've switched my eating schedule a little and experimented with another version of intermittent fasting, known as the condensed eating window. Essentially, this just means eating only during certain hours of the day. The difference to the 24/24 hour cycle is that the eating period does not continue onto the next day. A popularized version of this is the Fast-5 Diet, which promotes an eating window of 5 hours.

The way I do it is that I fast during morning and day and then break the fast when I get home from work. If I stop eating at midnight, this results in daily fasts of 16-18 hours and eating windows of 6-8 hours. So no breakfast and lunch but a big dinner and evening snacks.

There are various claims as to whether this kind of diet is healthy. One study suggested that eating only one big meal instead of the usual three may result in poorer insulin sensitivity and glucose tolerance and slightly higher blood pressure. On the other hand, body weight and stress hormone levels were reduced.

As discussed in the links above, the methodology of the study seems somewhat suspect. In any case, I won't be eating just one huge meal, but spread my energy intake throughout the 6 to 8 hours. For weight loss purposes eating only once per day may work, but I'm attempting to maintain my weight.

For more information on diets and health, see these posts:

Intermittent Fasting: Understanding the Hunger Cycle
Low-Carb vs. Low-Fat: Effects on Weight Loss and Cholesterol in Overweight Men
The Effects of a High-Fat Diet on Health and Weight: Does It Raise Cholesterol?
How Does Fructose Affect Triglyceride and Cholesterol Levels?

BioSil for Skin, Hair & Nails – Experiment Update

Beer contains 10-40 mg of silicon per litre. (Photo by Bernt Rostad)

For the past two and a half months, I've been taking 5 drops of BioSil. The active ingredient in BioSil is choline-stabilized orthosilicic acid, a bioavailable form of silicon. The reason behind the experiment is that BioSil was shown in one study to improve skin, hair and nail quality after 20 weeks.

While the women in the study used 10 mg, Natrol recommends to take 5 mg (equal to 5 drops) for hair, skin and nails, so I've stuck with the lower dosage so far. As for hair thickness, I haven't seen any visible difference yet. A microscopic analysis might show different results, but to the naked eye, there's been no change in the thickness of individual hairs.

It's difficult to compare results in skin quality, since I have so many other experiments going on at the same time (see my topical vitamin C experiment and lutein experiment for examples). The only change that I've noticed is perhaps a slight decrease in nail brittleness. I can't be certain, but my fingernails may be a bit thicker than they were. The rate of growth is unchanged, however.

Since I'm impatient and anxious to see results, I'm going to double my dosage and go for 10 mg per day. The taste is pretty vulgar even with 5 drops, but anything for the sake of science, right? I'll report back when I've finished the bottle, which should take about a month or so.

Oh, and if you've used BioSil and have noticed a difference, feel free to drop a comment and let me know how many drops you used.

For more information on skin, hair and nails, see these posts:

Examining Possible Causes for Slower Wound Healing
Coconut Oil Is Better than Olive Oil for Atopic Dermatitis
Hyaluronic Acid for Skin & Hair – Experiment Conclusion
Emu Oil and Hair Growth: A Critical Look at the Evidence

Swine Flu and Avoiding the Cytokine Storm: What to Eat and What Not to Eat?

Pomegranate juice is an ACE inhibitor. (Photo by JOE M500)

The scary connection between the 1918 flu pandemic (Spanish flu), the avian influenza (bird flu) and the swine influenza (pig flu) is that they all strike hardest those with healthy immune systems.

Usually, when people die of influenza, it's because they're old or their immune systems are compromised in other ways. Not so with the swine flu. As with the other two pandemics, death rates from swine flu have been highest among the 15-40 age group. Healthy young people seem to be in an especially big danger of dying from the influenza.

Swine flu, inflammation and the cytokine storm

The reason behind the deaths seems to be an exaggerated immune response, known as a cytokine storm. Since the body doesn't know what to do with the virus, it triggers an all-out release of inflammatory mediators. The reaction then becomes out of control, and the feedback loop ends up killing the patient (link).

The cytokine storm is the reason why the usual recipe for good health doesn't apply in the case of swine flu. Both inflammatory and anti-inflammatory cytokines have their uses in fighting off infection, and inhibiting inflammation is considered a good way to promote health in general. However, increasing anti-inflammatory cytokines during a cytokine storm is a bad idea.

So how do we shield ourselves from a cytokine storm? No one is really sure at this point. In a cytokine storm from avian influenza, the main cytokines responsible are TNF-alpha, IL-6 and IFN-gamma (link, link), with IP-10 and IFN-beta also being expressed more than usual (link). Reducing the levels of these and other cytokines could, at least in theory, be helpful. There is also some evidence that angiontensin converting enzyme (ACE) inhibitors might help in mediating cytokine storms (link, link, link), though we don't know for certain.

While taking cytokine and ACE inhibitors for swine influenza is currently only a theory, I nevertheless find it an interesting one. Specifically, I think a look into how "health foods" affect cytokines is useful, since conventional wisdom may not apply here due to reasons mentioned earlier. Below, we'll take a look at some natural cytokine and ACE inhibitors and also discuss which health foods may actually be harmful.

ACE inhibitors from natural sources

Procyanidins and flavanols have an inhibitory effect on angiotensin converting enzyme (link). They are found in many plants, such as apples, cocoa, cinnamon, berries and tea. Chokeberries have the highest concentration of procyanidins.

In one study, procyanidins and epigallocatechin were effective while catechin, epicatechin, gallic acid, chlorogenic acid, caffeic acid, quercetin, kaempferol and resveratrol at similar concentrations were ineffective (link). Accordingly, wine, chocolate and tea were all found to inhibit ACE activity, with red wine being more effective than white wine, green tea being more effective than black tea.

A word of caution: cocoa, while inhibiting ACE activity, may increase the secretion of TNF-alpha (link) and IL-1 and IL-4 expression (link), which could be bad news in the case of a cytokine storm. Chocolate may therefore not be a good idea if trying to reduce cytokines.

Quercetin, while ineffective in the study mentioned above, has been shown to have an inhibitory effect on the angiotensin converting enzyme, similarly to captopril (link), while also reducing blood pressure (link) and the angiotensin-induced production of IL-6 (link).

Another study found that both green tea and black tea inhibited ACE activity dose-dependently (link). In addition, all four catechins tested (including epicatechin) were effective. Rooibos tea, however, had no effect.

Pomegranate juice seems to be very effective in inhibiting ACE activity in vitro and in vivo (link). Hypertensive patients given 50 ml of pomegranate juice for two weeks had a 36% decrease in ACE activity and a 5% reduction in systolic blood pressure.

Cytokine inhibitors from natural sources

Epigallocatechin gallate (EGCG) inhibits the production of TNF-alpha, IL-6 and IL-8 (link). The best source of EGCG is green tea. Black tea is not without its merits either, though, as the theaflavins in black tea appear to reduce levels of IL-1 and IL-6 (link).

Several compounds in garlic appear to inhibit cytokines. Ajoene partially inhibits the production of TNF-alpha (link). Allicin inhibits IL-1, IL-8 and IP-10 (link), while alliin increases IL-1 and TNF-alpha (link). Crushing or chopping garlic causes alliin to be converted into allicin, while cooking garlic decreases allicin (link). Therefore, for the purposes of reducing cytokines, it's better to crush garlic and eat it raw.

Chronic garlic administration decreases myocardial TNF-alpha expression in rats (link). One study showed that garlic may increase IL-10 (link), and another one showed it increased IL-4 while reducing IFN-gamma (link). However, in humans, garlic powder extract has been shown to reduce IL-1 and TNF-alpha with no effect on IL-10 (link). The ratio of alliin and allicin may be important here as well.

When mice infected with influenza were fed vitamin E, they had significantly lower levels of IL-1beta, IL-6 and TNF-alpha (link, link). A relatively good natural source of vitamin E is red palm oil, which has been shown to reduce TNF in humans (link).

Fats, depending on their omega-3/omega-6 ratio and whether they're saturated or unsaturated, may play an important part in cytokine production. In rats, fish oil (which is high in omega-3) was shown to reduce levels of IL-1 and IL-6 (link). In humans, 4 weeks administration of flaxseed oil followed by 4 weeks of fish oil was shown to inhibit TNF-alpha and IL-1 in healthy humans, with fish oil being more effective (link).

Not all the data is positive, unfortunately. A long-term study comparing various doses of fish oil in humans concluded that supplementation for 1 year did not affect cytokine production (link). In another study, olive oil, coconut oil and fish oil all reduced IL-1 production in rats during the first 4 weeks of administration (link). However, after 4 weeks, olive oil and fish oil increased IL-6 production, and after 8 weeks, olive oil began to increase IL-1 production as well.

While resveratrol was found in the previously mentioned study to be ineffective for inhibiting ACE activity, it appears to suppress the expression of TNF-alpha, IL-6 and IL-8 (link, link). Resveratrol is found in red wine, red grapes and peanuts. Red wine has been shown to reduce levels of TNF-alpha, IL-6 and IL-8 in diabetics (link), although one study found no effect on cytokines from red wine (link) and another one found an increase in IL-6 (link). While those with peanut allergy should obviously avoid peanuts, it is unclear how peanuts affect cytokine levels in non-allergic people.

Quercetin decreases the expression of TNF-alpha, IL-6 and IL-8 (link, link). Food sources of quercetin include green tea, capers, fennel, onions, cocoa, kale and apples with skins (link, link). Compared to supplements, the quercetin content of foods is quite low, however.

Curcumin appears to reduce levels of TNF-alpha along with IL-6 and IL-8 (link, link, link). The main food source of curcumin is the spice turmeric. While the bioavailability of curcumin is very low, heating (link) and the addition of piperine greatly enhances its absorption (link). Piperine, which is found in black peppers, also inhibits inhibits IL-1, IL-6 and TNF-alpha (link).

One study showed that 2,000 IU of vitamin D3 given for nine months resulted in lower TNF-alpha and higher IL-10 levels than the control group (link). Vitamin D3 seems to increase IL-4 but decrease TNF-alpha, INF-gamma and IL-6 (link, link). On the other hand, a vitamin D deficiency reduced IL-1 levels, halved TNF levels and reduced IL-6 levels five-to-tenfold in mice (link). The Vitamin D Council newsletter covers this topic extensively (link); in short, they seem to advocate either not taking any vitamin D3 or taking at least 5,000 IU. Anything in between is potentially harmful for cytokine storms.

Summary

For the purposes of inhibiting ACE and reducing cytokines, the following foods and compounds seem to be the best choices:

• Green tea (ACE inhibitor, reduces cytokines)
• Black tea (ACE inhibitor, reduces cytokines)
• Quercetin (possible ACE inhibitor, reduces cytokines)
• Pomegranate juice (ACE inhibitor)
• Red wine (ACE inhibitor)
• Turmeric (reduces cytokines)
• Black pepper (reduces cytokines)
• Raw crushed garlic (reduces cytokines)
• Red palm oil (reduces cytokines)
• Vitamin E (reduces cytokines)
  
• Coconut oil (reduces cytokines)

The following foods, while beneficial in many other ways, may not be a good idea in terms of reducing cytokine levels:

• Olive oil (may increase cytokines)
• Fish oil (may increase cytokines)
• Chocolate (ACE inhibitor, increases cytokines)

In addition, it seems that vitamin D3 could be on either list, depending on the dosage. Average blood levels of vitamin D may be worse than very low or high levels.

That's it for this week, I'm off for a holiday (hopefully without swine flu), so no updates for a few weeks. For more information on cytokines and inflammation, see these posts:

Examining Possible Causes for Slower Wound Healing
Green Tea Protects from Arthritis in Rats
Green Tea Protects Cartilage from Arthritis in Vitro
Intermittent Fasting with a Condensed Eating Window – Part III: Fasting Blood Glucose, Cortisol & Conclusion

Soy Isoflavones Reduce DHT, Increase Testosterone

Soybeans contain the isoflavones genistein and daidzein. (Photo by T. Hagihara)

There's a lot of speculation on how soy intake and hair growth are related, so in a series of posts beginning with this one, we'll be taking a look at what the studies have to say. Hopefully, it will become clear whether soy isoflavones really do anything, how much isoflavones is the optimal intake, and whether oral or topical is the way to go.

In the first study we'll look at, male rats were fed soy isoflavones in various amounts (link). After a week, their testosterone and dihydrotestosterone (DHT) levels were measured. Since reducing DHT levels seems to be an effective way to reduce hair loss, this should be an interesting study for people considering soy isoflavones as a remedy.

Composition of the soy diets

To find out how soy isoflavones and androgen levels are related, the authors conducted two experiments. In the first experiment, rats in the treatment group were given soy flour with their normal chow. In the second experiment, rats in the treatment groups were given either a soy methanol extract or semipurified soy isoflavones.

The isoflavone content of the soy flour was 1.92 mg/g. The isoflavone contents of the soy methanol extract and semipurified soy isoflavones were 3.38 mg/g and 218 mg/g, respectively. In the first experiment, the rats in the treatment group received 442.7 g/kg soy flour in their diet. In the second experiment, they received 20 g/kg of soy extract or 2 g/kg of soy isoflavones in their diets.

Long story short, the according to the authors, the actual soy isoflavone intakes of the rats were as follows: 19 mg/day in the soy flour group, 0.9 mg/day in the soy extract group, and 3.3 mg/day in the soy isoflavone group. The control groups consumed zero soy isoflavones.

Soy isoflavones and DHT

Rats on the soy flour diet had significantly lower DHT levels than rats on the control diet. Similarly, the DHT levels of the rats on the soy isoflavone diet were about 60% lower DHT than in the control group. On soy extract diet DHT levels tended to decrease, but the difference was not statistically significant.


The figure above shows the DHT levels for the soy extract and soy isoflavone diets compared to the control group. The observed decrease in DHT from the soy flour diet (not shown above) was similar to that of the soy extract diet, with the exception that the difference was statistically significant.

Soy isoflavones and testosterone

Rats on the soy flour diet had similar levels of testosterone + dihydrotestosterone (T+DHT) as the control group. Since their DHT levels were lower, however, this means that there was an increase in testosterone from eating the soy flour diet. In the soy isoflavone diet, this effect was even clearer; not only was the reduction in DHT balanced by an increase in testosterone, but the total T+DHT levels were much higher than they were before the diet.



The figure above shows the T+DHT levels of the soy extract and soy isoflavone diets compared to the control group. Testosterone levels tended to increase and DHT levels tended to decrease also on the soy extract diet, but again, the differences were not statistically significant.

The fact that the soy isoflavone showed significant effects and the soy extract is possibly due to the differences in soy isoflavone content of the diets. The rats on the soy extract diet consumed only 0.9 mg/day, while those on the isoflavone diet consumed 3.3 mg/day. The two graphs shown here seem to support the idea that the effect is dose-dependent.

What is confusing, however, is that the soy flour diet showed a less pronounced effect than the soy isoflavone diet even though it had a much higher isoflavone content. Perhaps the dose-response is not linear but a bell curve. Unfortunately, the authors offer no explanation or theory for the results in the paper.

Conclusion

Soy isoflavones significantly reduced DHT levels and increased testosterone levels in male rats. An intake of 3.3 mg of isoflavones per day was the most effective of the three treatments tested. A lower intake showed similar but less pronounced effects, while a higher intake did not appear to further add to the effect.

For more information on hair growth, see these posts:

Tea Tree Oil vs. Korean Red Ginseng – Hair Growth Battle Conclusion
North African Plant Extract (Erica multiflora) Increases Hair Growth
Bioactive Form of Silicon (BioSil) Improves Skin, Hair & Nails in Photoaged Women
2% Nizoral Shampoo Increases Hair Growth More than 2% Minoxidil