Vitamin D Receptor Polymorphisms in Chronic Telogen Effluvium (CTE)

Certain Vitamin D Receptor Changes May Increase the Risk of Chronic Shedding in Women

The role of vitamin D in human health is the subject of tremendous research interest - and also great controversy and debate. Some experts actually say we are focusing way too much on the role of vitamin D nowadays …. and some say we need to focus more. The same is true for the role of vitamin D in the hair follicle.

It’s clear that vitamin D has some sort of role. Vitamin D binds to the vitamin D receptor (or “VDR”) and together this complex sits on various genes and tells the genes what to do. The vitamin D receptor is expressed in the dermal papilla of the hair follicle as well as in epidermal keratinocytes. VDR expression increases in hair follicles in late anagen and catagen phases. Individuals with mutations in the VDR develop complete hair loss - an indication that vitamin D singling in hairs is important. What is less clear is how vitamin D affects hair loss in adults.

Vitamin D receptor polymorphisms (VDR polymorphisms) refer to subtle changes in the genes coding the vitamin D receptor. These are often one or two nucleotide changes that ever so slightly change the vitamin D receptor gene and/or the way the vitamin D receptor gets manufactured in the body. Studies have focused on whether these subtle changes in the VDR (i.e. VDR polymorphisms) affect various aspects of human health. From colon cancer to heart disease, these VDR receptor polymorphisms are an intensively researched topic.

VDR Receptor Polymorphisms in Chronic Telogen Effluvium

Seliet and colleagues from Egypt set out to determine if two VDR polymorphisms have any role in chronic shedding - or what is typically called chronic telogen effluvium (CTE). They studied 30 women with chronic telogen effluvium and 30 controls who did not have chronic telogen effluvium. The specific VDR polymorphisms that were studied were the Taq1 and the Cdx1 polymorphisms.

Results are shown in the table below. Remarkably, the CC genotype of the Taq1 and then GA genotype of the Cdx1 were associated with increased risks of women having chronic shedding. The highest was for the CC genotype of the Taq1 where a 15 fold increased risk of CTE was found.

Polymorphisms in the VDR. the CC genotype of Taq1 confers a 15 fold increased risk of CTE.

Conclusion

This work is interesting. It seems that certain polymorphisms increased the risk of hair shedding in women. Growing research over the years has taught us that some polymorphisms affects the stability and activity of VDR mRNA and protein. Furthermore, it does seem that many patients who don’t response well to vitamin D supplementation may in fact have these sorts of vitamin D receptor polymorphisms. For example, studies have shown that women with certain VDR polymorphisms can improve their bone mass with vitamin D supplementation and women with other VDR polymorphisms do not.

Moving forward

A common question I am asked is whether we can just test for these VDR polymorphisms. That answer is ‘not yet’. Testing for these is not something we do routinely …. and it’s still in the realm of ‘research only’. I am also asked if taking more vitamin D is going to help if one actually has these polymorphisms or simply if one has chronic telogen effluvium. We don’t know those answers either. Certainly if one has low vitamin D levels (as measured by the 25 hydroxy-vitamin D test), taking more vitamin D is going to be quite reasonable.

Reference
Seleit I et al. Vitamin D Receptor Gene Polymorphism In Chronic Telogen Effluvium; A Case-Control Study. Clin Cosmet Investig Dermatol. 2019 Oct 8;12:745-750. doi: 10.2147/CCID.S227232. eCollection 2019.

L-lysine: It's role in iron and zinc absorption

It's Role in Iron and Zinc Absorption

L-lysine is an amino acid and is found in eggs, meat, fish and eggs. Generally speaking, lysine is one of the more challenging amino acids to get through normal food intake. This is especially true for those who do not consume these products.

There are very few studies looking at the role of L-lysine and hair. However, there is one in particular that one should be aware of. These are studies focusing on the role of L-lysine in iron and zinc absorption. In 2002, D.H. Rushton showed benefits of l-lysine in increasing iron and zinc levels and in reducing hair shedding.

Among 14 zinc deficient women, L-lysine at doses 1000-1500 mg daily led to an increase in zinc levels from 9.7 to 14.6 umol/L even without these women consuming actual zinc pills.

Similarly, Rushton showed L-lysine may help iron absorption. In his study, iron pills (100 mg per day) in 7 women with chronic telogen effluvium did not change ferritin levels at all. However, when combined with L-lysine (again at 1000-1500 mg per day), ferritin levels increased from 27.4 to 58.6 ug/L. This reduced hair shedding causing the proportion of hairs in the telogen phase to decrease from 19.5 to 11.3.

L-lysine is a key amino acid and I often add it to the overall plan for patients with chronic shedding abnormalities and those with deficiencies of iron and zinc that don't respond to standard treatments. If I do ultimately recommend patients use L-lysine, the dosing in our clinic is typically 500 mg twice daily, and rarely three times daily for short periods.
 

Reference

DH Rushton. Nutritional factors in hair loss. Clin Exp Dermatol 2002
 

Vitamin D Levels in Alopecia Areata

Does low vitamin D levels play a role in alopecia areata?

Several previous studies have explored this topic. A new study compared vitamin D levels in 50 patients with AA compared to 35 age matched and sex matched controls. 25-hydroxy-vitamin D levels were lower in patients with AA being 16.6 in the AA group and 40.5 in the control group. 25-hydroxy-vitamin D is the best test for vitamin D status. In addition, patients with more severe AA had lower vitamin D levels than those with less severe AA. Also, those with more patches of AA had lower levels than those with fewer patches.
 

Conclusion 

This study adds to the growing body of evidence showing the vitamin D plays a role in alopecia areata. 

Reference 

Bhat YJ et al. Vitamin D Level in Alopecia Areata. Indian J Dermatol. 2017 Jul-Aug.

Alopecia areata: A close look at selenium and zinc

What are the most common abnormalities of serum trace elements in alopecia areata?

New data confirms a role for zinc and emphasizes an interesting potential role for selenium.

A study from China set out to investigate the alterations of serum level of trace elements and AA using a meta-analysis of ten published articles involving 764 subjects. Overall, lower serum levels of zinc and selenium were identified compared to healthy controls. However, there was no significant difference between the AA patients and controls in the levels of serum copper, ferritin, magnesium. and copper. 

These studies point to a potential role for selenium and zinc in alopecia areata. This warrants further study.

Reference

Jin W, et al. J Dermatol. 2017. Changes of serum trace elements level in patients with alopecia areata: A meta-analysis.

What doses of the B vitamins are needed?

The role of the B vitamins is not entirely clear. For some vitamins, such as biotin and vitamin B12, it seems that unless one is truly deficient in the particular vitamin, supplementation is not going to help.

Whether that is true for all the B vitamins is not clear. It certainly may be that some B vitamins are beneficial for hair growth even if the patient has normal levels. In patients with excessive shedding (telogen effluvium) in which an underlying cause can not be found, I often recommend 50-100 mg of vitamin B5 (pantothenic acid) and the same dose of B6.

Administration of vitamin B5 and vitamin B6 appear to have some benefits in human and animal studies.

Biotin and Hair Loss

Why Does the World Love Biotin So Much?

Biotin is a well-known and popular supplement for treating hair loss. Let's face it - the world loves biotin. However, true deficiencies in biotin are rare given the ability of bacteria in the gastrointestinal system to produce biotin. Nevertheless, many individuals and physicians turn to biotin in the search for treatment options. 

Soleymani and colleagues from New York University School of Medicine set out to critically examine the evidence for biotin use for treating hair loss. Their findings point out that there are no randomized trials to support the use of biotin in treating hair loss and that the public’s interest in biotin over the past decades is not supported by medical evidence. 

There is really no evidence to support routine biotin supplementation for individual’s with hair loss. Exceptions do exist, of course, and true biotin deficiency may be considered in individuals who are elderly, pregnant, using anticonvulsants or chronically using alcohol. 

Reference

Soleymani T et al. J Drugs Dermatol. 2017 May 1;16(5):496-500

Methotrexate dosing in Children: How much ?

Methotrexate in Children with Alopecia areata

Methotrexate is sometimes used as a treatment for children with alopecia areata. Generally, topical steroids, minoxidil are used first followed sometimes by diphencyprone (DPCP) and/or anthralin as second line agents. Methotrexate in my clinic tends to be a third line agent but in some situations I will use it before DPCP and anthralin. 

Methotrexate is an immunosuppressant. It inhibits the proliferating of rapidly dividing immune system cells.  Studies of children aged 8-18 years with alopecia areata have suggested that benefit is seen in about 40 % of children who use methotrexate. 

Methotrexate Dosing in Children. 

The dose of methotrexate is discussed on a case by case basis. Generally, the dose to use depends on the child's weight. Doses in the range of 0.2 to 0.7 mg of methotrexate for every kilogram of body weight are not uncommon. The medication is only given once per week, and must never be used daily.

I generally start with 2.5 - 5 mg and slowly move upwards every week until the desired dose is obtained. For example, for a 70 pound child (31.8 kg), the dose range is 6.36 mg to 22.2 mg. I would generally start 2.5 mg in the first week and then 5 mg in the second week and then 10 mg in the third week and then 15 mg in the fourth week. One can move up faster if they wish, but this is my preference, especially in children under 10 years of age. 

Side effects of Methotrexate

Many children tolerate methotrexate well. Nausea is the most common side effect and tends to occur on the particular day of the week that the medication is taken (methotrexate is not used every day). Sometimes vomiting can occur. Other side effects include lowered blood counts, irritation of the liver, and cough from irritation of the lungs. 

I try hard to reduce nausea and especially vomiting in children taking methotrexate. Sometimes when children develop vomiting from Methotrexate then become extremely fearful of taking the medication. Administration of anti-nausea medications before taking the methotrexate can really help. About 25-30 % of children will have significant nausea with their methotrexate and 10 % will experience vomiting. 

Folic acid with Methotrexate

Folic acid is a vitamin which is prescribed every day except on the day that the child takes the methotrexate pill. The use of folic acid has been shown to reduce the chances of the child having changes in his or her blood counts and reduces the chance of the medication irritating the liver. 

Reference

Royer M, et al. Efficacy and tolerability of methotrexate in severe childhood alopecia areata. Br J Dermal 2011;165(2):407-10.

Biotin and the hair

Biotin for Hair: Yes or No?

One of the top 50 questions I am asked is whether biotin supplements should be used. The short answer is really that there is no good evidence that biotin does much for most people. It is however, quite safe and overdosing is unlikely provided one sticks to 5000 mcg or less per say. 

Is anyone biotin deficient?

However, the following groups may be more likely to have biotin deficiency: 

1. individuals with intestinal issues,

2. women who are pregnant, 

3. individuals taking anti-seizure medications, chronic antibiotics, or isotretinoin

4. individuals who consume alcohol chronically

5. those with inborn errors of metabolism

6. the elderly 

7. those with extremes of poor diet

In those who are recommended to take biotin, type of biotin supplement does not appear to matter. 1000 mcg twice daily to up to 2500 mcg is appropriate dosing for most. Once should never exceed 5000 mcg. I always advise individuals to review this question with their physician an avoid unnecessary supplementation.

Organic Meats, Health and Hair

Hair, Meat and Protein Intake

Hair is made up of protein. So to no surprise, my attention often shifts to the quantity and quality of protein in my patient's diets. There has been a remarkable increase in demand for organic food in the past 2 decades. There is a perception that organic farming is more sustainable, has better nutritional and health value, is kinder to animals. 

Studies to date have started to show differences in the nutritional value of organic meats. Some studies have suggested organic meat is higher in beneficial omega 3 fatty acids (which may reduce the risk of cardiovascular disease). Organic meats may have lower concentrations of the saturated fatty acids myristic- and palmitic acid (which were linked to an increased risk of cardiovascular disease). Whether other vitamin, mineral and micronutrients truly differ in organic vs conventional meats is not clear. Furthermore, and perhaps, most importantly we do not yet have a clear understanding of the impact of chronic antibiotic and hormone use in conventional livestock on the health benefits of humans. More studies are needed in these areas to better understand the magnitude of effect of health issues such as obesity, insulin resistance, fertility, heart disease and cancer. While these are clearer broad issues, they have important implications for how hair loss develops and how we treat hair loss. If possible, I do recommend that many of my patients who do eat meat consider substituting organic meats where possible.

Reference
Composition differences between organic and conventional meat: a systematic literature review and meta-analysis. Średnicka-Tober D, et al. Br J Nutr. 2016.

Food safety and organic meats.
Review article. Van Loo EJ, et al. Annu Rev Food Sci Technol. 2012.

More Pieces to the Vitamin D Puzzle

More Pieces to the Vitamin D Puzzle

At least once a day, I’m asked about the role of vitamin D in hair loss. Back in July, I wrote a blog article about the role of vitamin D in hair loss.   Vitamin D does its job inside cells by binding to the vitamin D receptor or VDR.

How important is vitamin D in helping prevent hair loss in humans?

Modern science still doesn’t have all the answers. But by turning to research in mice, we have learned a lot or valuable lessons.  About 10 years ago, we learned that hair loss develops in mice that lack the vitamin D receptor (VDR). Researchers in San Francisco recently discovered a molecule called MED1 which helps the action of the vitamin D receptor. In fact, the researchers found that if they blocked the actions of MED in mice those mice grew less hair. The research findings were recently discussed on the NBC today's show:

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These data suggest that defects in MED1 or defects in vitamin D signaling could potentially be involved in the development of certain types of hair loss – but more research is needed.

CONCLUSIONS

1. Vitamin D has an important role in hair growth – mice that lack the vitamin D receptor (VDR) develop hair loss and mice that lack an activator of the VDR (called MED) develop hair loss

2. It’s more complicated than simply taking more vitamin D pills. Don’t think for a minute that popping more vitamin D pills is going to lead to more hair growth.

REFERENCES

Xie et al. Lack of the vitamin D receptor is associated with reduced epidermal differentiation and hair follicle growth. J Invest Dermatol 2002; 118: 11-6.

Oda Y et al. Coactivator MED1 Ablation in Keratinocytes Results in hair Cycling Defects and Epidermal Alterations. Journal of Investigative Dermatology 2012; 132: 1075-83