A condition, known commonly as "black urine disease" or Alkaptonuria is a rare genetic disorder involving protein metabolism, and it has its root in the mutation of the homogentisate 1,2-dioxygenase gene, which in turn causes homogentisic acid accumulation in the body. The appearance of dark urine after exposure to air is due to this kind of accumulation; however, a variety of symptoms can be expected, such as joint stiffness, changes in pigmentation, and other long-term health complications. Although the prevalence has been estimated to be between 1 in 250,000 and 1 in 1 million people in the United States, its effects are indeed high on those affected.

Alkaptonuria is an autosomal recessive disease, meaning that the child must inherit a defective copy of the HGD gene from both parents. If both parents are carriers, their offspring have a 25% chance of inheriting two faulty genes and developing alkaptonuria. The condition is genetic but is often not diagnosed for years because it progresses slowly and its early symptoms appear to be harmless.

Symptoms of Alkaptonuria

The most characteristic and common initial symptom of alkaptonuria is dark urine. The reason for this is due to the fact that excess HGA is excreted in the urine and upon oxidation in the presence of air, it gives the urine a brown or black color. Though it is often considered cosmetic, the long-term accumulation of HGA within the connective tissues produces more complicated health problems.

Progressive joint pain and stiffness: The accumulation of HGA in cartilage leads to early-onset osteoarthritis, making movement increasingly difficult over time.

Skin and eye pigmentation changes: Affected individuals may develop bluish or grayish discoloration of the sclera (white part of the eye) and the skin, particularly in areas exposed to friction.

Cardiovascular and respiratory problems: With age, HGA accumulation can lead to valve calcifications in the heart and stiffening of connective tissues in the respiratory tract, which can cause problems in middle and old age.

Decreased mobility and spinal problems: The spine may become stiff and painful due to chronic cartilage degeneration.

These symptoms usually begin to manifest during adulthood, leading to severe complications in a person's 40s or 50s and significantly affecting the quality of their life.

How is Alkaptonuria Diagnosed?

Because of its rarity, alkaptonuria is often mistaken or overlooked early in life. However, there are several ways to confirm the condition:

Urine Testing: The gold standard in the diagnosis is the testing of urine samples for high levels of homogentisic acid via gas chromatography. In case of oxidation, which changes the color of urine to black, it is indicative of alkaptonuria.

Genetic Testing: Confirmatory genetic testing reveals mutations of the HGD gene to diagnose the condition conclusively.

Blood Tests: High levels of HGA in the blood can be used as further evidence.

Imaging Studies: X-rays and MRIs will expose cartilage and joint damage characteristic of alkaptonuria.

Management of Alkaptonuria: Is There A Cure?

At present, there is no cure for alkaptonuria; however, various treatment approaches can reduce its symptoms and slow the disease's progress:

Nitisinone Therapy: Nitisinone is a drug that inhibits the production of HGA. It has been shown to reduce HGA levels and slow tissue damage. However, it needs to be taken under close medical supervision because of potential side effects.

Low-Protein Diet: Since HGA is a byproduct of protein metabolism, reducing protein intake—especially foods rich in tyrosine and phenylalanine—may help decrease HGA production.

Pain Management: OTC pain relievers and anti-inflammatory medications can be used to relieve joint pain and stiffness.

Physical Therapy: Exercise regularly, as it may improve mobility and strengthen muscles, thus reducing strain on affected joints.

Surgical Interventions: Most people with alkaptonuria develop severe osteoarthritis necessitating joint replacement in their old age. Also, some may require heart valve replacement surgery if cardiovascular complications develop.

Life with Alkaptonuria

Although alkaptonuria is not fatal, it severely affects the quality of life. The progressive deterioration of the joints and associated symptoms can make everyday activities difficult, requiring lifestyle changes and medical interventions. The disease may cause premature aging of the joints, requiring walking aids and mobility assistance earlier than expected.

Ongoing research will continue to work on improving the treatment options by focusing on gene therapy and alternative enzyme replacement therapies. However, because of its rarity, the clinical trials and research remain sparse.

As genetic research advances, more hope for better management and possible curative approaches for alkaptonuria exists. Scientists are searching extensively for enzyme replacement therapies and innovative drugs that can target the root cause of the disorder. Being aware and being diagnosed early helps individuals better their condition and ultimately have better long-term health outcomes.

Alkaptonuria is a striking example of how one gene mutation can have widespread effects on the body. Though still a rare and often misunderstood condition, growing awareness and advances in treatment are paving the way for better care. If you or a loved one suspect symptoms of alkaptonuria, it is essential to seek early diagnosis and medical guidance to manage the disease effectively and preserve quality of life.

Permanent hair dyes promise vibrant, long-lasting colour, but many contain a hidden risk: a chemical called p-phenylenediamine, or PPD. While essential for keeping hair shades bold, PPD has been linked to allergic reactions, skin inflammation, and, in rare cases, life-threatening poisoning. Experts warn that even everyday use can trigger unexpected skin issues, making awareness and caution crucial for anyone coloring their hair.

PPD in Hair Dyes: What You Need to Know

Most permanent hair dyes sold in the US and Europe contain an ingredient called p-phenylenediamine (PPD), an aromatic amine. This chemical is essential for keeping hair colour long-lasting and resistant to washing or drying. However, research increasingly links PPD to severe allergic reactions, potential cancer risks, and even life-threatening poisoning.

How PPD Affects Your Skin

Even in normal cosmetic use, the body absorbs only small amounts of PPD, but it can still trigger a variety of health issues. Allergic reactions and contact dermatitis are the most common. About 72 hours after exposure, PPD can provoke immune sensitization and inflammation, which may show up as redness, swelling, blisters, and intense itching.

People with pre-existing skin conditions such as eczema, dandruff, or other rashes are more susceptible. While 1.5% of the general population may react to PPD, this rises to 6% among those already prone to dermatitis.

PPD and Cancer Risk

The International Agency for Research on Cancer (IARC) classifies occupational exposure to hair dye as “probably carcinogenic,” but personal use hasn’t been conclusively linked to cancer. A 36-year study in 2020 found no strong association between regular hair dye use and most cancers, although it noted potential links to specific types, including estrogen receptor-negative breast cancer and basal cell carcinoma. Experts caution that these findings are not definitive and require further investigation.

Life-Threatening Risks of PPD Poisoning

While cosmetic exposure carries minimal systemic risk, ingesting PPD can be deadly. Oral exposure can cause rapid multi-organ failure, with initial signs including unpredictable swelling of the neck and airways, known as angioneurotic edema. Even with medical intervention, the mortality rate for severe PPD poisoning is around 14.5%.

Safer Alternatives and Precautions

Rising awareness of PPD’s risks has prompted the development of PPD-free dyes using alternatives like p-toluenediamine sulfate (PTDS). However, research shows that about half of individuals allergic to PPD may also react to PTDS.

The safest way to reduce risk is by performing a patch test 48 hours before every use. Professional users should wear protective gloves, and improved consumer education on potential sensitivities can further minimize danger.

How To Check If You’re Allergic To PPD

Finding out if you’re sensitive to PPD is relatively straightforward. You can visit an allergy clinic for a professional assessment, or do a patch test at home before applying any PPD-based hair dye.

What To Watch For On The Label?

PPD may appear under different names on hair dye packaging. Look out for any of the following terms, as they all indicate the presence of PPD:

• P-phenylenediamine
• Para-phenylenediamine
• 4-aminoaniline
• 1,4-benzenediamine
• p-diaminobenzene

COVID-19 and influenza are major causes of illness and death worldwide, particularly in countries like the US and UK. Vaccines can prevent infection or reduce the severity of illness, yet many people struggle to stay up to date due to time constraints or lack of motivation. If you are eligible for both vaccines around the same time, combining them in a single visit can save time and effort.

Doctors suggest that receiving both vaccines at the same visit can be a convenient approach, but a common question arises: which arm should you use? Is it safe to administer both vaccines in the same arm, or is it better to use separate arms?

One Arm or Two: Which One To Use For Both Shots?

Getting both shots in one visit sounds efficient, but you still need to decide whether to use one arm or two. Often, it comes down to personal preference, although sometimes the healthcare provider will make the decision. Is there evidence to guide this choice? Should both vaccines go in the same arm or one in each?

Which Arm Works Best for COVID and Flu Vaccines?

Animal studies suggest that administering the COVID and flu vaccines in the same limb may enhance immune responses. The mRNA COVID vaccines include a built-in immune booster called an ionizable lipid, which is a fatty molecule that protects the mRNA inside the vaccine.

Flu vaccines usually lack an adjuvant, but the built-in adjuvant in the COVID shot could potentially boost the flu vaccine’s immune response if both are given in the same arm.

However, giving two shots in one arm can increase the risk of arm soreness, the most common side effect. To explore this in humans, researchers at the University of Melbourne conducted a randomized controlled trial with 56 healthy adults. The study compared giving the Moderna COVID mRNA vaccine and the CSL influenza vaccine in the same arm versus opposite arms.

Participants were randomly assigned to two groups: the “same arm” group received both vaccines in the non-dominant arm (usually the left arm for right-handed people), while the “opposite arm” group had the COVID vaccine in the non-dominant arm and the flu vaccine in the dominant arm. This setup was chosen because the COVID vaccine is more likely to cause a sore arm compared to the flu shot. Researchers collected blood, saliva, and nasal samples, and participants reported on any side effects.

Same Arm vs. Opposite Arm

The trial found no significant differences in key immune responses, such as neutralizing antibodies, whether the vaccines were given in the same arm or separate arms. Secondary analyses suggested a slightly higher immune response to COVID in the opposite arm group.

Nearly all participants reported mild arm soreness. Those in the same-arm group experienced more tenderness in that single arm, while participants in the opposite-arm group had reactions in both arms, particularly in the non-dominant arm that received the COVID vaccine.

What This Means for You

Overall, receiving both vaccines on the same day, whether in one arm or two, provides strong protection against both infections. Choosing opposite arms may slightly improve immune response and reduce soreness in any one arm, but it comes with two mildly sore arms.

For anyone looking to save time, having both vaccines in the same visit is convenient and effective. Most side effects are mild, making the benefits of dual vaccination well worth it.

Although herbs and plants have been used for medicinal purposes for thousands of years, they have recently gained a surge in popularity, partly thanks to TikTok posts where users highlight the benefits of supplements such as ashwagandha, turmeric, and green tea.

While many consider herbal supplements “natural,” this does not automatically make them safe. Unlike prescription medicines, they do not require approval or review from the U.S. FDA before hitting the market. Users may experience side effects, and some herbs can interfere with medications they are already taking.

Can Herbal Supplements Cause Liver Damage?

Some herbal supplements can harm the liver. A recent study from the University of Michigan suggests that around 15.6 million adults in the U.S., about 5% took at least one herbal supplement in the last 30 days that may be harmful to the liver, known as hepatotoxic. This study was published in JAMA Network Open.

6 Potentially Hepatotoxic Botanical Products

Researchers analyzed data from over 9,500 U.S. adults, with an average age of 47.5, who participated in the National Health and Nutrition Examination Survey (NHANES) between 2017 and 2020. They examined participants’ use of both prescription medications and herbal supplements.

The study focused on six herbal supplements previously linked to liver toxicity:

• Ashwagandha
• Black cohosh
• Garcinia cambogia
• Green tea extract
• Red yeast rice
• Turmeric or curcumin

“Potentially hepatotoxic botanical products contain plant-based ingredients that may contribute to liver damage,” explained Alisa Likhitsup, MD, MPH, a clinical assistant professor in the Department of Internal Medicine at the University of Michigan and lead author of the study.

“How these supplements cause liver injury isn’t fully understood, but it likely involves how the liver metabolizes these products,” she added.

Data from the Drug Induced Liver Injury Network show liver injuries linked to botanical products have risen from 7% in 2004–2005 to 20% in 2013–2014.

‘Natural’ Doesn’t Always Mean Safe

After reviewing the study, Rosario Ligresti, MD, FASGE, chief of Gastroenterology at Hackensack University Medical Center in New Jersey, said that while hepatotoxic botanical products are derived from plants, the lack of oversight and testing means they may do more harm than good.

“They’re unregulated before reaching the market, so it’s not surprising that they pose significant health risks, especially to the liver. They can interfere with the liver’s ability to process and detoxify substances, potentially leading to toxin buildup, inflammation, cell death, and, in severe cases, liver failure,” Ligresti explained, as per Medical News Today.

One notable case involved a 57-year-old woman in New Jersey and New York who developed severe liver damage after taking 2,250 mg of turmeric daily since March 2025 which is far above the WHO’s safe limit of 0–3 mg per kg of body weight per day. She required hospital care for six days at NYU Langone.

Signs of liver damage can include fatigue, nausea, loss of appetite, stomach pain, and dark urine.

Ligresti emphasized that physicians should routinely ask patients about their use of herbal supplements and discuss potential liver risks.