Who Actually Runs Low on Biotin? Accutane, Valproate, Pregnancy and Raw Egg Whites, by the Evidence

Who Actually Runs Low on Biotin? Accutane, Valproate, Pregnancy and Raw Egg Whites, by the Evidence

Watch: Who Actually Runs Low on Biotin? — video

By Jack Zheng, MS Pharmacy — Founder of MIHIYO Labs

Summary

Isotretinoin (Accutane) may lower the activity of biotinidase, the enzyme that recycles biotin, and evidence for valproate (Depakote) is mixed; neither has been shown to make most users biotin deficient. In 42 acne patients, biotinidase activity fell from 4.70 to 2.50 nmol/min/L after 30 days of isotretinoin, while serum biotin did not change significantly. Inherited biotinidase deficiency, large amounts of raw egg white and chronic alcohol exposure are well-established risk factors, and biomarker studies suggest marginal insufficiency in pregnancy. MIHIYO Labs' 10-in-1 hair oral dissolving strip (ODS) provides 5,000 mcg of supplemental biotin, without claims that it improves hair in people with adequate status or offsets drug side effects.

MIHIYO Labs' 10-in-1 Hair Growth Strip contains 5,000 mcg of biotin. If you take isotretinoin, valproate or any other prescription medicine, talk to your prescriber before adding it, and see the lab-test note further down.

Why ask who runs low, instead of whether biotin works?

In a 2017 review of 18 published cases reporting hair or nail improvement with biotin, every patient had an underlying condition.9 That makes identifying a possible deficiency or other cause more useful than assuming extra biotin will improve hair growth in otherwise healthy people.

I covered the efficacy question in does biotin help hair growth: in people without a deficiency, controlled evidence for a hair benefit is lacking. So this article looks at the groups people search for most: people on isotretinoin, people on valproate, pregnant women, and people who eat raw egg whites or carry an inherited enzyme defect.

This is the fifth article in a 20-part series on the ten ingredients in our hair formula, after vitamin B12, vitamin D, zinc and silica.

What does biotinidase do, and why do drug studies measure it?

Biotinidase is the enzyme that frees biotin from proteins so the body can reuse it, and a low biotinidase level is not the same thing as low biotin.

Biotin works as a cofactor for carboxylase enzymes. When those enzymes are broken down, biotin is still attached; biotinidase cuts it loose so it can be recycled. People born with very little biotinidase activity develop skin rash and hair loss, among more serious problems, unless they take biotin.7 That is why drug studies measure the enzyme: if a medicine lowers biotinidase, a recycling problem becomes plausible.

Plausible is not proven. Serum biotin can stay normal while enzyme activity falls,1 and researchers who study marginal deficiency rely on functional markers such as urinary 3-hydroxyisovaleric acid or lymphocyte propionyl-CoA carboxylase activity, which are not routine tests.6 When you read "drug X causes biotin deficiency", check which of these was actually measured.

Biotinidase recycles biotin, and the routes to low biotin act at different points Biotin from food is used as a cofactor by carboxylase enzymes. When those enzymes are broken down, biotin is still attached to protein, and the enzyme biotinidase frees it so it can be reused. Isotretinoin and valproate have been linked to lower biotinidase activity in some studies, although serum biotin did not change in the isotretinoin study. Raw egg white contains avidin, which binds biotin and reduces how much is available; cooking inactivates it. Inherited biotinidase deficiency breaks the recycling step from birth. How the body reuses biotin, and where the "low biotin" routes act Simplified. Lower enzyme activity is not the same thing as low biotin. Biotin from food free biotin absorbed Carboxylase enzymes use biotin as a cofactor Enzymes broken down biotin still protein-bound Biotinidase frees biotin for reuse reused Routes to low biotin, and what was measured Isotretinoin, valproate Lower biotinidase in some studies; serum biotin unchanged in the isotretinoin study Inherited biotinidase deficiency Recycling step impaired from birth; found by newborn screening, managed with biotin Raw egg white (avidin) Binds biotin from food; thorough cooking inactivates avidin Pregnancy Marginal status by enzyme and urine markers; hair was not measured

Can you take biotin while on Accutane?

In a 42-patient study measuring both biotinidase activity and serum biotin, isotretinoin was associated with lower biotinidase activity after 30 days, while serum biotin did not change significantly.1

Schulpis and colleagues in Athens followed 42 patients with severe cystic acne on isotretinoin monotherapy at 0.5 mg/kg a day. On day 30, biotinidase activity had fallen from 4.70 to 2.50 nmol/min/L, also lower than in 50 untreated controls (5.2). Serum biotin showed no significant change. When the researchers mixed the drug directly with the enzyme in a test tube, activity did not drop, so they proposed an effect on the liver, where biotinidase is made.1

What this supports: isotretinoin affects the enzyme that recycles biotin. What it does not support: "Accutane makes you biotin deficient." The study had no hair endpoint, lasted only 30 days, and found no significant change in serum biotin. However, unchanged serum biotin alone cannot rule out functional biotin insufficiency.

A second study tested biotin alongside the drug. Aksac and colleagues gave 60 acne patients isotretinoin at 0.5 mg/kg a day; half also took 10 mg of biotin a day for four months. The biotin group's anagen (growing) hair ratio rose and telogen (resting) ratio fell versus its own baseline, and skin hydration did not drop as it did in the isotretinoin-only group.2 There was no placebo, the abstract does not describe blinding, and the dose was twice what our strip contains. These findings primarily describe changes within the treatment groups. They do not, by themselves, establish a statistically significant between-group benefit attributable to biotin; larger randomized, placebo-controlled trials would be needed. I read it as a hypothesis, not as a reason to add biotin to a course of isotretinoin on your own.

My practical view: if you are on isotretinoin and want to take any biotin-containing supplement, ask the dermatologist who prescribed it. They may also be ordering blood tests during the course, and biotin can interfere with some of them.10

Does Depakote (valproate) cause biotin deficiency and hair loss?

Hair loss on valproate is well recognized, but whether low biotin is the reason is unsettled: studies of biotinidase in valproate users point in opposite directions.

  • For a link. In 75 children with seizures, Schulpis and colleagues found biotinidase activity significantly lower in the two higher-dose groups than in 50 healthy children after 45 days of valproate, and lower activity tracked higher blood levels of the drug.3 The same Athens group ran the isotretinoin study above.
  • Against. Castro-Gago and colleagues measured serum biotin and biotinidase in 20 children on valproate, 10 on carbamazepine and 75 controls, and found no significant differences in either. Three children on valproate lost hair with normal biotin, zinc and biotinidase levels.4
  • The newest adult data. Kakunje and colleagues compared 75 adults on valproate (93% for bipolar disorder) with 75 controls in a cross-sectional study. Hair loss was reported by 24% of the valproate group and 2.7% of controls. Mean biotinidase was 2.96 versus 3.68 nmol/min/mL, and participants who reported hair loss had lower biotinidase than those who did not.5 Hair loss was recorded from verbal reports, serum biotin was not measured, and a cross-sectional design cannot show which came first.

Both pediatric studies report hair improvement following biotin supplementation at 10 mg a day.34 Notably, the three children with alopecia in Castro-Gago's study had normal serum biotin, zinc and biotinidase activity before supplementation.4 These uncontrolled observations cannot establish that biotin caused the improvement or that it prevents valproate-associated hair loss.

Valproate is prescribed for epilepsy, bipolar disorder and migraine.5 Stopping it or changing the dose on your own can be dangerous. If you notice shedding on valproate, tell your prescriber; that conversation, not a supplement, is the first step.

Are pregnant women low in biotin?

Studies of biochemical markers suggest that marginal biotin insufficiency may occur during otherwise normal pregnancies. However, abnormal biomarkers do not necessarily establish clinically significant biotin deficiency, and these studies did not evaluate hair outcomes.6

Mock's 2009 review reports that about half of pregnant women excrete more 3-hydroxyisovaleric acid, a marker of reduced activity of a biotin-dependent enzyme, although pregnancy itself changes kidney function, which complicates that marker. In a pilot study, a second marker, lymphocyte propionyl-CoA carboxylase activity, was low in 18 of 22 pregnant women, and rose in all 4 who were given biotin.6 The concern about birth defects in that review comes from mouse studies.6

That is a reason for obstetric care to take biotin status seriously. It is not evidence that biotin changes hair shedding in pregnancy, and it does not tell you what dose to take. If you are pregnant, follow your obstetrician's advice on supplements. Also tell them about any biotin you take: FDA notes that prenatal multivitamins can contain biotin and that hormone tests are among those that can be affected.10 I go through the evidence on laboratory hCG (pregnancy hormone) assays in biotin and blood tests.

What about raw egg whites and inherited biotinidase deficiency?

Both are well-established causes of biotin deficiency, although they are uncommon in everyday life. Other recognized risk factors include chronic alcohol exposure, which inhibits biotin absorption, and pregnancy and breastfeeding.12

Raw egg whites. Egg white contains avidin, a protein that binds biotin and reduces its availability; thorough cooking inactivates it.7 Researchers use this to induce marginal deficiency on purpose: in an outpatient study, five people who drank egg-white beverages with enough avidin to bind about 7 times their estimated dietary biotin developed marginal deficiency by standard markers within 28 days.8 That was a deliberate, high-avidin protocol. Cooked eggs are not the issue.

Inherited biotinidase deficiency. This autosomal recessive condition is picked up by newborn screening in many places. Untreated profound deficiency, under 10% of normal enzyme activity, usually shows up between one week and ten years of age with seizures, low muscle tone, hair loss and skin rash. People with partial deficiency (10-30%) may have symptoms only under stress such as infection. It is managed with lifelong oral biotin under a specialist.7

Who runs low on biotin: the evidence side by side

Group What was measured Main finding Design and size What it does not show
Isotretinoin (Accutane) Biotinidase activity, serum biotin Enzyme 4.70 to 2.50 nmol/min/L at day 30; serum biotin unchanged Before-and-after, 42 patients, 50 controls1 Biotin deficiency; any hair outcome
Isotretinoin plus 10 mg biotin Hair ratio by dermoscopy, skin hydration Higher anagen and lower telogen ratio versus baseline in the biotin group Two groups of 30, no placebo2 A placebo-controlled effect; anything about 5,000 mcg
Valproate, children Biotinidase activity Lower at higher doses in one study; no difference in another 75 vs 503; 20 vs 754 Agreement between studies; low serum biotin
Valproate, adults Biotinidase, self-reported hair loss Hair loss 24% vs 2.7%; lower enzyme in those reporting it Cross-sectional, 75 vs 755 Cause and effect; that biotin prevents it
Pregnancy Urinary 3HIA, lymphocyte enzyme activity About half with raised 3HIA; enzyme low in 18 of 22 (pilot) Review of biomarker studies6 Any hair outcome; a dose
Raw egg white Standard biotin status markers Marginal deficiency induced within 28 days Experimental, 5 people8 Risk from cooked eggs
Inherited biotinidase deficiency Enzyme activity, genetics Rash and hair loss among symptoms when untreated Clinical review7 Relevance to adults with normal screening
Isotretinoin lowered biotinidase activity in 30 days, but serum biotin did not change significantly In 42 patients with severe cystic acne taking isotretinoin 0.5 mg/kg a day (Schulpis 1999), biotinidase activity fell from 4.70 nmol/min/L before treatment to 2.50 nmol/min/L on day 30, compared with 5.2 nmol/min/L in 50 untreated controls. Serum biotin showed no significant change. The study did not measure hair. Isotretinoin: the enzyme dropped, serum biotin did not Serum biotinidase activity, nmol/min/L; 42 patients on isotretinoin 0.5 mg/kg/day, 50 untreated controls Source: Schulpis et al., Skin Pharmacology and Applied Skin Physiology 1999 Untreated controls 5.2 Patients, before 4.70 Patients, day 30 2.50 (P < 0.001 vs before) Serum biotin: no significant change over the same 30 days. Hair was not measured. Lower recycling-enzyme activity is not the same as biotin deficiency.

What clues point to real biotin deficiency rather than everyday shedding?

In clinically significant biotin deficiency, especially untreated inherited biotinidase deficiency, hair loss can occur alongside skin rash and other symptoms.7 However, mild or marginal deficiency may not produce these classic signs.

The isotretinoin and valproate papers both describe partial biotinidase deficiency as producing seborrheic dermatitis-like skin changes alongside hair loss,13 and the inherited condition lists skin rash with alopecia.7 In the 2017 review, all 18 published cases of hair or nail improvement with biotin had an underlying condition.9 These signs are not specific to biotin, and medication-associated hair loss does not by itself show that biotin is low. So shedding plus a scaly rash, in someone with one of the risk factors above, is a reason to see a clinician rather than to self-diagnose. Ordinary shedding with no rash and no risk factor calls for a look at other causes first, such as iron deficiency, thyroid disease, recent illness or stress, and pattern hair loss; a dermatologist can work out which applies.

Where this fits in MIHIYO Labs' 10-in-1 strip

MIHIYO Labs' 10-in-1 Hair Growth Strip combines 5,000 mcg biotin with zinc, copper, vitamin D3, B5, B6, B12, folate, bamboo silica and apple procyanidin B2. I sort those ingredients by job rather than as one "stack", and explained in ingredient synergy why I avoid the word synergy for them.

Biotin sits in the coenzyme group alongside B5 and B6, which support normal metabolic processes relevant to skin and hair physiology. The formula provides 5,000 mcg of biotin per strip, but this dose has not been shown to improve hair growth in people with adequate biotin status. It is not there on a "more is better" theory, and I explained why we chose 5,000 rather than 10,000 mcg in 5,000 vs 10,000 mcg.

The evidence grade I give biotin for hair is "helpful when deficient; no controlled evidence of benefit in people who are not". Nothing in this article shows that the MIHIYO Labs hair strip offsets the effects of isotretinoin, valproate or any other medicine, and it has not been tested in a clinical trial. It is a nutritional formula, not a treatment for hair loss, and it contains no iron.

Because the strip contains 5,000 mcg of biotin, tell your doctor you take a biotin-containing supplement before any blood draw. FDA has warned that biotin can cause falsely high or falsely low results on some lab tests, including hormone tests,10 and its current troponin page still lists heart-test assays that can read falsely low in the presence of biotin.11 How long to pause depends on the dose and the test, so follow the laboratory's instructions.

What are the honest limits of this evidence?

Almost everything here measures enzymes or biomarkers, not hair, and most of it comes from small, uncontrolled or cross-sectional studies.

  • The isotretinoin enzyme finding comes from a 42-patient, 30-day study in which serum biotin did not change.1
  • The two studies that found lower biotinidase on isotretinoin or valproate came from the same research group,13 and an independent pediatric study found no difference.4
  • The adult valproate study is cross-sectional, relied on verbal reports of hair loss and did not measure biotin.5
  • Pregnancy data are biomarkers; the hair question was not studied.6
  • For people with adequate biotin status, there is still no randomized trial showing that extra biotin improves hair.9

Practical takeaways

  • On isotretinoin: the drug can lower biotinidase, but serum biotin did not change significantly in the 42-patient study discussed above. Talk to your prescriber before adding biotin.
  • On valproate: report new shedding to your prescriber. Do not stop or change the dose on your own.
  • Pregnant: follow your obstetrician on supplements, and mention biotin before any blood test.
  • Raw egg whites in large amounts can bind biotin; cooked eggs do not.
  • Shedding with a scaly rash and a known risk factor deserves a clinician's look.
  • If your hair formula contains biotin, tell your doctor and the lab before blood work.
  • That is the role MIHIYO Labs gives biotin in its 10-in-1 strip: providing supplemental biotin without claiming that a higher intake produces better hair growth or treats medication-related hair loss.

Frequently asked questions

Can you take biotin while on Accutane?

Ask the dermatologist who prescribed it. Isotretinoin lowered biotinidase activity in a 42-patient study, but serum biotin did not change significantly, and biotin can interfere with some blood tests your prescriber may order during treatment.

Does Depakote cause hair loss because of low biotin?

It is not established. One pediatric study found lower biotinidase on higher valproate doses, another found no difference, and an adult cross-sectional study linked self-reported hair loss to lower biotinidase. No controlled trial in the studies I reviewed has shown that biotin prevents valproate-associated hair loss.

What are the signs of biotin deficiency?

Biotin deficiency can cause hair thinning, a scaly skin rash and, in severe inherited cases, neurological symptoms. These signs are not specific to biotin deficiency, and their absence does not completely rule out marginal deficiency. A clinician should assess the person's risk factors and other possible causes.

Do cooked eggs block biotin?

No. Avidin, the biotin-binding protein in egg white, is inactivated by thorough cooking.

References

  1. Schulpis KH, Georgala S, Papakonstantinou ED, Michas T, Karikas GA. The effect of isotretinoin on biotinidase activity. Skin Pharmacology and Applied Skin Physiology. 1999;12(1-2):28-33. PMID: 10325581 / DOI: 10.1159/000029843. https://pubmed.ncbi.nlm.nih.gov/10325581/
  2. Aksac SE, Bilgili SG, Yavuz GO, Yavuz IH, Aksac M, Karadag AS. Evaluation of biophysical skin parameters and hair changes in patients with acne vulgaris treated with isotretinoin, and the effect of biotin use on these parameters. International Journal of Dermatology. 2021;60(8):980-985. PMID: 33682085 / DOI: 10.1111/ijd.15485. https://pubmed.ncbi.nlm.nih.gov/33682085/
  3. Schulpis KH, Karikas GA, Tjamouranis J, Regoutas S, Tsakiris S. Low serum biotinidase activity in children with valproic acid monotherapy. Epilepsia. 2001;42(10):1359-1362. PMID: 11737173 / DOI: 10.1046/j.1528-1157.2001.47000.x. https://pubmed.ncbi.nlm.nih.gov/11737173/
  4. Castro-Gago M, Pérez-Gay L, Gómez-Lado C, Castiñeiras-Ramos DE, Otero-Martínez S, Rodríguez-Segade S. The influence of valproic acid and carbamazepine treatment on serum biotin and zinc levels and on biotinidase activity. Journal of Child Neurology. 2011;26(12):1522-1524. PMID: 21642615 / DOI: 10.1177/0883073811409227. https://pubmed.ncbi.nlm.nih.gov/21642615/
  5. Kakunje A, Prabhu A, Karkal R, Pookoth KR, Kumar P, Gupta N, Priya ES, Nishad P. Study of association between valproic acid levels, biotinidase activity and hair loss in Indian population: A cross-sectional comparative study. Indian Journal of Psychiatry. 2025;67(9):894-899. PMID: 41019267 / DOI: 10.4103/indianjpsychiatry_1152_24. https://pubmed.ncbi.nlm.nih.gov/41019267/
  6. Mock DM. Marginal biotin deficiency is common in normal human pregnancy and is highly teratogenic in mice. Journal of Nutrition. 2009;139(1):154-157. PMID: 19056637 / DOI: 10.3945/jn.108.095273. https://pubmed.ncbi.nlm.nih.gov/19056637/
  7. Wolf B. Biotinidase Deficiency. In: Adam MP, et al., editors. GeneReviews. Seattle (WA): University of Washington, Seattle; 2000 (updated February 19, 2026). PMID: 20301497. https://pubmed.ncbi.nlm.nih.gov/20301497/
  8. Stratton SL, Henrich CL, Matthews NI, Bogusiewicz A, Dawson AM, Horvath TD, Owen SN, Boysen G, Moran JH, Mock DM. Marginal biotin deficiency can be induced experimentally in humans using a cost-effective outpatient design. Journal of Nutrition. 2012;142(1):22-26. PMID: 22157538 / DOI: 10.3945/jn.111.151621. https://pubmed.ncbi.nlm.nih.gov/22157538/
  9. Patel DP, Swink SM, Castelo-Soccio L. A Review of the Use of Biotin for Hair Loss. Skin Appendage Disorders. 2017;3(3):166-169. PMID: 28879195 / DOI: 10.1159/000462981. https://pubmed.ncbi.nlm.nih.gov/28879195/
  10. U.S. Food and Drug Administration. UPDATE: The FDA Warns that Biotin May Interfere with Lab Tests: FDA Safety Communication. Issued November 5, 2019 (updating the November 28, 2017 communication). Archived copy accessed via the Internet Archive. https://web.archive.org/web/20201221055709/https://www.fda.gov/medical-devices/safety-communications/update-fda-warns-biotin-may-interfere-lab-tests-fda-safety-communication
  11. U.S. Food and Drug Administration. Biotin Interference with Troponin Lab Tests — Assays Subject to Biotin Interference. Content current as of June 21, 2022. https://www.fda.gov/medical-devices/in-vitro-diagnostics/biotin-interference-troponin-lab-tests-assays-subject-biotin-interference
  12. National Institutes of Health, Office of Dietary Supplements. Biotin: Fact Sheet for Health Professionals. Updated January 10, 2022. https://ods.od.nih.gov/factsheets/Biotin-HealthProfessional/

By — Founder of MIHIYO Labs. Focused on the R&D of high-bioavailability, fast-absorption oral dissolving strips.

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