Soy Isoflavones Grow Hair by Increasing IGF-1 in the Skin

Food sources of isoflavones include tofu and miso soup. (Photo by sokole oko)

Many of you have probably heard that soy isoflavones may be good for hair loss. How exactly dietary isoflavones work to promote hair growth is less clear, however.

As long-time readers may remember, I've written before about the effects of dietary isoflavones on humans and animals. For example, in male rats even a relatively low amount of soy isoflavones reduces DHT and increases testosterone. This alone would probably be enough to explain hair growth in rodents.

Of course, humans are a more difficult case. Most of the things that show promise in mice or rats don't work for humans with androgenic alopecia in the end. The good news is that soy isoflavones reduce DHT even in humans. The bad news is that the reduction may not be great enough. About 60 mg of isoflavones daily reduced serum DHT in healthy young men by only 15%.

Even this moderate drop would suggest a reduction in 5-alpha-reductase, which converts testosterone to DHT. However, the markers of 5-alpha-reductase looked at in the study did not show a difference between the treated and the control group.

And yet, a combination of capsaicin and soy isoflavones grows hair in both animals and humans. In this study, capsaicin injected into the skin was enough to grow hair in animals, although the combination was more effective. In humans, orally administered isoflavones and capsaicin resulted in hair growth in 88% of the participants with androgenic alopecia, which is a remarkable result for a supplement that reduces DHT by so little.

The authors speculated that capsaicin and soy isoflavones promote hair growth by increasing dermal levels of insulin-like growth factor (IGF-1). They suggested that a key factor was calcitonin gene-related peptide (CGRP), which acts as a vasodilator, among other things. It also increases IGF-1 in various tissues, including the skin.

This theory is supported by the fact that subcutaneous capsaicin increased CGRP release and IGF-1 expression in hair follicle cells in normal mice but not in CGRP-knockout mice. Soy isoflavones increased the production of CGRP, which explains why the combination was more effective than capsaicin alone.

Based on these studies, it was still unclear whether dietary isoflavones alone promote hair growth. Now, the same authors have investigated their idea further. In their new study, they fed isoflavones to mice whose backs were shaved and measured their hair growth (link). Again, both wild-type mice and CGRP-knockout were used.

The isoflavone supplement used was Fujiflavone P40, which contains 43.5% isoflavones. 5 g of the product was mixed per each kg of standard chow. On average, the mice ate 4.6 grams of food daily, which means that their daily intake of isoflavones was 0.0046 * 0.005 * 0.435 = ~10 mg (correct me if my calculation is wrong).

After three weeks of isoflavone administration, dermal CGRP and IGF-1 levels in wild-type mice increased significantly compared to the control group. In the knockout mice, no difference was seen between mice given isoflavones and the control group.

Hair follicle number also increased in wild-type mice given isoflavones. Compared to the control group, they had about 40% more hair follicles. The knockout mice had less hair follicles to begin with, and when they were given isoflavones, no improvement was seen. Thus, it seems that isoflavones grow new hairs through increasing dermal levels of CGRP and IGF-1.

Compared to the mice given isoflavones, the control mice seemed to take a longer time growing their existing hair back. Even the knockout mice that saw no increase in IGF-1 grew their hair back quicker when they were given isoflavones. This might be due to other effects of isoflavones, such as reducing DHT levels. Based on the pictures in the full paper, the wild-type mice grew their hair back even quicker, however. Wild-type mice given isoflavones also had a more pronounced darkening of hair than their control group.

So what is the take home message? Based on all these studies, it looks like soy isoflavones show very good potential for promoting hair growth. A part of their effectiveness may come from the fact that they reduce serum DHT and increase testosterone, but based on the rodent data, the real kick is from the increase in skin levels of IGF-1.

At the moment, there is no data comparing the effectiveness of soy isoflavones vs. capsaicin in humans. However, we do know that the combination is superior in increasing dermal IGF-1 in animals, and that the combination of both taken orally grows hair in humans with androgenic alopecia.

For more information on hair growth, see these posts:

Topical Retinoids Increase Hair Growth in Most People
BioSil, JarroSil & Beer – Silicon Experiment Conclusion
Zinc Pyrithione Reduces Shedding and Moderately Promotes Hair Growth
Hair Growth with Ayurveda – The Nutrich Oil Experiment

Selegiline and Lifespan Extension

Deprenyl increases the lifespan of female hamsters. (Photo by MarinaAvila)

Selegiline, also known as deprenyl, is an old life extension drug. It's been around since the 80's, but after some conflicting data from Parkinson's Disease studies, interest in selegiline for life extension purposes has been negligible.

These days, deprenyl is mostly used to treat Parkinson's Disease, depression and dementia. Still, the early studies showed such promising results that a review of the studies on deprenyl and longevity is in order.

Deprenyl extends maximum lifespan in male rats

In the first study on selegiline and lifespan, 24-month old male Wistar-Logan rats were treated subcutaneously with selegiline (0.25 mg/kg) or saline solution three times a week (link). The control group receiving only saline had an average lifespan of 147 weeks, about 34 months. The longest living rat in this group was 164 weeks (~37 months) old.

The deprenyl group did significantly better. In fact, even the shortest living rat receiving selegiline managed to outlive the longest living in the control group, making it to 171 weeks (~39 months). The longest living rat survived for a whopping 226 weeks (~52 months). That's a maximum lifespan increase of 38%. The average lifespan in the deprenyl group was 198 weeks (~46 months). The author, Dr. Joseph Knoll, states:

The average lifespan was higher than the estimated maximum age of death in the rat (182 weeks). This is the first instance that by the aid of a well-aimed medication members of a species lived beyond the known lifespan maximum.

In 1994, Dr. Knoll continued his experiments, again using the same dosing but this time on younger Wistar-Logan rats (28 weeks, or ~6 months old), some of which were sexually inactive and some of which were sexually highly active (link).

The sexually inactive control rats remained inactive throughout their life and lived 135 weeks (~31 months), whereas their deprenyl-treated peers suddenly developed a hunger for sex and lived 152 weeks (~35 months), the same as the sexually active control group. The highly active rats given deprenyl became even more sexually active than their saline-treated control group, and lived for 185 weeks (~43 months).

Only mean lifespan increases in another strain of rats

Between Knoll's experiments on male Wistar-Logan rats, another lifespan experiment on selegiline was done. This time, male Fischer rats were given deprenyl (0.25 mg/kg) or saline subcutaneously every other day, starting at 23 to 25 months of age (link).

Again, the deprenyl group lived longer, but this time the effect was not as dramatic as in the previous study. The remaining life expectancy of rats given selegiline was increased by only 16%. Then again, as Ben Best points out in his good summary of deprenyl, Fischer rats live only 28 months, much shorter than Wistar-Logan rats.

In 1993, Japanese scientists doubled the standard dose of deprenyl and injected male Fischer rats with 0.5 mg/kg, starting from the age of 18 months (link). The abstract states:

The increases in average life expectancies caused by deprenyl treatment (15% from 18 months and 34% from 24 months) were both statistically significant.

I don't have access to the full paper, so I'm not sure what exactly they mean by this. Were there actually two treated groups, with one given deprenyl since 18 months and the other since 24 months of age, or did the control group start dropping dead faster after 24 months?

In any case, maximum lifespan was apparently not increased, unlike in the previous studies. A possible explanation is the shorter lifespan of Fischer rats and the higher dose used. On the other hand, Ben Best says on his website:

At the 2004 American Aging Association Conference Kitani (one of the authors of the Fischer study) reported that he had halved the dose to the standard 0.25mg/kg (3 times per week) and increased mean life span 44% for females and 32% for females starting from 24 months. Nonetheless, no significant increase in maximum lifespan was seen.

If the above is correct, then the higher dose is probably not the culprit. Perhaps treatment has to be begun earlier, or perhaps deprenyl doesn't work in all rat strains.

Different doses and forms of deprenyl

In 1992, two more studies appeared in a Hungarian journal, with Dr. Knoll as the coauthor in both of them. The first one fed male mice either deprenyl, Dinh lang root extract or a combination of the two three times a week, starting at 12 months of age (link). The abstract states only that the combination was the most potent treatment, increasing both memory function and survival time.

The second study used the same dosage of deprenyl as before, but this time 6-month old male Wistar rats and a different form of deprenyl known as (-)p-fluoro-deprenyl were used (link). The study lasted for 25 months. Three of the 20 control rats (15%) and 15 of the 40 deprenyl-treated rats (37.5%) survived until the end. Three of the rats receiving selegiline were still sexually active at 31 months, even though normal male Wistar rats lose their ability to ejaculate by the time they're 2 years old.

The authors also experimented with a much smaller dose of selegiline, giving 13-month old non-copulator rats only 0.01 mg/kg instead of the usual 0.25 mg/kg. The lifespan of these rats was short, with the control group living only 102 weeks (~23 months) and the (-)p-fluoro-deprenyl group living 106 weeks (~24 months). Rats given the standard deprenyl lived for 104 weeks. Sexual performance was improved in both deprenyl groups, however.

Deprenyl in females, mice, and dogs

The first study on selegeline and life extension on female rats came a few years later. Once again, the dosing was 0.25 mg/kg injected three times a week (link). The rats were 6 months old and had their ovaries removed. All the control females were dead before hitting 15 months of age, while all of the deprenyl-treated rats were still alive. Three of them even reached 36 months of age. Unlike in the case of males, however, neither group showed much sexual activity.

In Syrian hamsters, a low dose of selegiline increased the lifespan of females but not males, even though MAO-B was inhibited in both groups by the same amount (link). Female controls died younger than male controls, but in the deprenyl group this difference disappeared.

Deprenyl seems to increase lifespan also in immunosuppressed mice. When 4 mg of selegiline was mixed in 10 kg of feed, survival improved dramatically (link). The last mouse in the control group died 2.5 months after the study was started, at the age of 5 months, whereas the last mouse in the selegiline group made it to 14.5 months.

Deprenyl and dogs

Rodents are not the only animals that seem to gain extra years from selegiline. A study on beagle dogs, ranging in age from 2.8 to 16.4 years, studied the effects of orally administered deprenyl on lifespan (link). The dose was 1 mg/kg, four times as high as the one originally used by Dr. Knoll on rats.

The study lasted for 2 years and 10 weeks. Almost all of the young dogs survived until the end of the study, but older dogs given deprenyl survived longer than those that were given placebo. 80% of dogs in the deprenyl group survived until the end of the study, compared to only 39% in the placebo group. The first deprenyl-treated dog died on day 247, whereas the first untreated dog died on day 295.

Summary

In the experiments of Dr. Knoll, who first discovered its life-extending properties, selegiline consistently increased the mean and maximum lifespan of male Wistar-Logan rats. The rats given deprenyl had a maximum lifespan that was up to 38% greater than that of the control rats. The longest living rat in these studies was 52 months old. Only one study looked at female rats and life extension, but it too showed an increased lifespan from deprenyl.

Extrapolating directly from rats, the 0.25 mg/kg dose used in the experiments would correspond to 20 mg of selegiline every other day, or 10 mg daily, for a man weighing 80 kg (~176 pounds). For a female weighing 60 kg (~132 pounds), the equivalent would be 7.5 mg daily.

Not all of the results have been so uniformly positive, however. While mean lifespan was increased in male Fischer rats, maximum lifespan was not. One possible reason is the shorter average lifespan of Fischer rats, but other explanations cannot be ruled out. Also, male Syrian hamsters given deprenyl did not live longer, although females did.

For more information on life extension, see these posts:

Does Intermittent Fasting Increase Lifespan?
How Do People Feel about Life Extension?
Dietary Supplement Increases Lifespan by 11% in Healthy Mice
Slowing Down Aging with Intermittent Protein Restriction

Topical Retinoids Increase Hair Growth in Most People

Retinoids – slap them on your scalp and let nature do the rest. (Photo by Steve Rhode)

Retinoid creams and gels are probably the most effective skin care products out there at the moment. They seem to do just about everything you could hope for: increase skin firmness and hydration, reduce wrinkles, improve skin tone, you name it. But what about hair growth?

The effects of retinoids on hair growth have been much less studied, even though the positive data on skin health suggests they might rejuvenate scalp skin also. My own experiment with retinol (the milder cousin of retinoids) and the resulting new hairs certainly supports this idea.

And yet, while my ongoing experiment with tretinoin has visibly improved my skin, I can't say I've seen much of an increase in hair growth. I find this somewhat surprising, given that tretinoin is much stronger than retinol. Time to take a look at what the science says on retinoids and hair growth.

The earliest paper I could find compared the effects of various treatments on hair regrowth in mice (link). According to the paper, retinoic acid applied topically was the least effective of the three treatments but still caused some hair regrowth after shaving the backs of the mice. Interestingly, UV irradiation was more effective, while estradiol suppressed hair regrowth.

Then, in 1986, a group of scientists decided to try topical retinoids and minoxidil on humans with androgenic alopecia (link). After one year of using the combination, 66% of the participants saw regrowth of terminal hairs. None of the participants used minoxidil alone, but some of them did use only retinoids. Applying 0.025% tretinoin topically resulted in hair growth in 58% of the subjects. The picture below shows one subject before and after using tretinoin.


According to the authors, the hair growth may be due to increased cell proliferation and differentation and the generation of new blood vessels. Another paper that appeared a few years later also speculates on how retinoids might cause hair growth (link). The authors of this paper suggest that certain retinoids increase the rate of hair of hair growth, prolong the anagen phase, and help convert vellus hairs to terminal hairs.

At least in mice, levels of cellular retinoic acid binding protein are higher during the anagen phase and lower during the telogen phase of hair growth. Applying some retinoids topically increases the level of this protein in the skin, which might explain how retinoids prolong the growth phase (link). Both isotretinoin (also called 13-cis-retinoic acid) and tretinoin (also called all-trans-retinoic acid) seem to shorten the telogen phase and increase the anagen phase; however, they also differ in their effects, at least in vitro (link).

A review on retinoids and hair growth states that according to the studies, only tretinoin and isotretinoin are able to prolong the anagen phase (link). I'm not sure how true this statement is, given that other vitamin A derivatives such as etretinate have been associated with hair darkening and new hair growth (link) and even retinol boosts the effectiveness of minoxidil (link).

Not all studies have found the combination of minoxidil and retinoids to be superior to minoxidil alone (link). The hypothesis that retinol and some retinoids increase the absorption of minoxidil is plausible, but this is not the only explanation, since retinoids are effective even on their own. Thus, with or without minoxidil, retinol and retinoids seem worth a shot. Keep in mind, though, that the picture above shows the result after one year of use, and that almost half of the participants did not see an increase in hair growth.

For more information on hair growth, see these posts:

Zinc Pyrithione Reduces Shedding and Moderately Promotes Hair Growth
Hair Growth with Ayurveda – The Nutrich Oil Experiment
Do Flax Lignans Reduce Hair Loss from MPB?
Green Tea Extract Grows Hair in Vitro, Might Work in Vivo