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The dark spell of Chucky on Alice It was a gloomy night in the small town as Alice walked home alone. The wind howled through the trees, causing a chill to run down her spine. She couldn't shake the feeling that someone was watching her. As she reached her front door, a sense of relief washed over her. She quickly unlocked the door and stepped inside, eager to escape the darkness outside. However, little did she know that the darkness had followed her home.

The supplement is called Not Today, Grey by the company Arey. A post on Arey’s Instagram profile refers to their “initial studies” (plural) apparently showing benefits like slowing down the greying process and making the hair feel more full and healthy. When I casually reached out to them to inquire about these studies, I was told about a single study of 30 participants aged 30 to 53. This study was internal and is not publicly available. Therefore, we have no way of knowing exactly how the study was conducted, what the full results were, or even if there was a control group. Before-and-after photos posted on the website of three study participants contain quotes about hair feeling thicker and being “better” (whatever that means), but we have no idea if these participants did anything else to their hair during the study. It is also possible that some of these participants had a medical condition that affected the state of their hair and that receiving treatments for this condition actually explains the improvement in hair quality during the Arey study. We simply do not know, and these are not trivial questions: good science is about minimizing the impact of stray variables and zeroing in on the specific question we are asking. Otherwise, we run the risk of deceiving ourselves.

The amounts of vitamins and minerals are not necessarily equivalent while both the multivitamin I had on hand and Arey s supplement contain 55 micrograms of selenium, the latter has nearly twice the amount of vitamin B6 as the former. The idea that Mother Nature gives us clues as to the benefits of a plant by shaping it a certain way like walnuts should be good for brain health because they look like little brains comes from sympathetic magic and is not supported by our scientific understanding of the world.

However, little did she know that the darkness had followed her home. Alice had always been fascinated by the supernatural. She would often spend her evenings reading books about ghosts, witches, and curses.

The Pill That Promises to Delay the Grey

The website has a subtle grey background. The banner image shows an elated young woman with dark hair streaked with reddish-brown, basking in the sunlight. The company’s proposition is bold: “delay the grey.” Why put up with grey hair when we could pop a new pill to “replenish [our] body with the vitamins, minerals and anti-oxidants” it needs to hold onto our natural hair colour?

The company is called Arey, a name derived from the French word for stop, arrêt, although the pronunciation is different. The way they market their supplement reminded me of hims, the wellness outfit that wants to be goop for men. There’s a contemporary vibe to the Arey website, a casual minimalism that doesn’t take itself too seriously. It’s aspirational but it also tries to be relatable. Their product came to my attention recently and I was asked, “What do you make of this?”

Whether a pill can slow down the greying of our hair depends in part on what we know about why our hair goes grey in the first place.

A bit of a grey area

The colour of human hair is due to the ratio between a couple of molecules: the black-brown eumelanin and the reddish-brown pheomelanin. The relative quantities of these two pigments will decide our natural hair colour, from jet black to brown to blond to red. Our hair has cells that are dedicated to producing these pigments: they are called melanocytes.

There comes a time, however, when this pigmentation starts to wane and our hair looks grey. The Scrabble crowd will be delighted to know that there are two scientific names for this greying of the hair. From the Latin, we have canities (pronounced “kuh-NISH-eez”), while the Greek language gave us achromotrichia, which literally translates to a lack of colour in the hair.

You may have heard of the 50-50-50 rule—that 50% of us will have had 50% of our hair turn grey by the age of 50—but a large study reveals this to be an overestimation, with between 6 and 23% of people sporting a half-and-half by the age of 50. Europeans and their descendants tend to go grey before Asians and Africans, and some people’s hair goes grey prematurely at a much younger age. While scientists can’t agree on a clear age cut-off for what constitutes premature hair greying, they have discovered a number of risk factors for it, which include smoking, certain vitamin deficiencies, and genetics, because premature hair greying can run in families.

When our hair has lost its pigmentation, the colour can come back. There is the striking case of a 68-year-old Japanese man whose hair was practically all white, but following the administration of a therapeutic antibody for persistent inflammation of the skin, half of his hair reverted back to its natural black colour. His case is a dramatic but rare example of repigmentation. Earlier this year, a team of researchers published the results of a study in which they looked at plucked hairs from 14 healthy participants. They saw hairs that had initially turned grey but that then started expressing their natural colour again. The tip of the hair was grey but the part closer to the scalp was pigmented. This reversal of the greying process was seen across a wide range of ages (from 9 to 39), in both men and women, in different ethnic groups, and not just for scalp hair but pubic and beard hair as well. The bad news is that this repigmentation was limited to rare, isolated hairs. It seems there might be a window before old age when a few hairs can do this, but apart from the unusual case of the Japanese man above, we are a far cry from significantly reversing the greying process.

By now, you may be wondering what exactly causes our hair to lose its colour as we age, and scientists would like to know as well. It turns out we do not fully understand the underlying process. The natural loss of pigmentation over time can be influenced by a long list of factors, including diseases like progeria and metabolic syndromes, conditions like vitiligo, and deficiencies in vitamins and minerals. But studies of hair greying have provided evidence to spawn a few hypotheses, and it may well turn out that all of these ideas are correct and that hair greying is a complex phenomenon fed by multiple biological processes.

One such hypothesis points the finger at oxidative stress. The hype over antioxidants brought a lot of attention to this phenomenon. Basically, our body naturally produces molecules called free radicals that readily react with other molecules. These free radicals can cause a lot of damage but they are kept in check by antioxidants. If the balance between these two classes of molecules favours the free radicals, however, we get oxidative stress and its resulting damages. Studies have shown that the very process of creating the pigments in our hair generates a lot of oxidative stress. Combined with other internal sources of oxidative stress, like inflammation and psychoemotional stress, and external sources, like ultraviolet radiation, we get a buildup of oxidative stress over decades that may cause our melanocytes, the pigment-producing cells, to age and die off.

But other studies have pinned the blame not on the melanocytes directly but on their progenitors, the melanocyte stem cells. If antioxidants are so 2005, stem cells are the new frontier in hype. Stem cells are undifferentiated cells in our body that go on to specialize in order to play a specific role, like a baby growing up to be a dispatcher or a biologist. One hypothesis to explain hair greying is that the pool of melanocyte stem cells gets exhausted over time, either because of damage done to the DNA or because of the oxidative stress that results from producing the hair pigments.

The bottom line is that, for one reason and/or another, our hair eventually loses its natural colour. Can a new supplement give us a deferment?

Vitamins and a little something for your liver

The supplement is called Not Today, Grey by the company Arey. A post on Arey’s Instagram profile refers to their “initial studies” (plural) apparently showing benefits like slowing down the greying process and making the hair feel more full and healthy. When I casually reached out to them to inquire about these studies, I was told about a single study of 30 participants aged 30 to 53. This study was internal and is not publicly available. Therefore, we have no way of knowing exactly how the study was conducted, what the full results were, or even if there was a control group. Before-and-after photos posted on the website of three study participants contain quotes about hair feeling thicker and being “better” (whatever that means), but we have no idea if these participants did anything else to their hair during the study. It is also possible that some of these participants had a medical condition that affected the state of their hair and that receiving treatments for this condition actually explains the improvement in hair quality during the Arey study. We simply do not know, and these are not trivial questions: good science is about minimizing the impact of stray variables and zeroing in on the specific question we are asking. Otherwise, we run the risk of deceiving ourselves.

Not Today, Grey contains, among other things, vitamins and minerals, like vitamin B12 and iron. If you’re worried about your vitamin intake, you can get a multivitamin for much cheaper, in the neighbourhood of 16 cents a day, whereas Not Today, Grey costs between 57 and 67 cents a day depending on whether or not you get the monthly subscription. The amounts of vitamins and minerals are not necessarily equivalent: while both the multivitamin I had on hand and Arey’s supplement contain 55 micrograms of selenium, the latter has nearly twice the amount of vitamin B6 as the former. But I’m curious to know why these specific amounts were chosen. After all, the authors of a 2020 systematic review of the evidence on pharmacotherapy and reversal of hair greying stated that “no randomized controlled trial has addressed the issue of its therapy,” and another 2020 review concluded that studies of premature hair greying and the amount of minerals found in the blood—minerals like iron, zinc, copper and calcium—yielded inconsistent results and that additional studies are needed to know if supplementing with these minerals makes a difference.

Of course, Not Today, Grey is not simply a multivitamin and mineral supplement. It contains other components, such as para-aminobenzoic acid (PABA). PABA, also known as vitamin B10, has generated some interest with regards to reversing premature hair greying, but a 2020 systematic review summarized the evidence for PABA alone or in combination with calcium pantothenate (which Not Today, Grey also contains) as a weak recommendation because of limited-quality, patient-oriented evidence. Not exactly a ringing endorsement. But there is one more component of Not Today, Grey that really caught my eye.

It’s called Fo-Ti, although it has other names like polygonum multiflorum and he shou wu. Fo-Ti is a flowering plant, and Arey’s blog announces that the legend surrounding the plant’s discovery is a “testament to the ‘doctrine of signature’ - the concept that a plant resembles the condition or part of the body it will benefit.” This is the first red flag. The idea that Mother Nature gives us clues as to the benefits of a plant by shaping it a certain way—like walnuts should be good for brain health because they look like little brains—comes from sympathetic magic and is not supported by our scientific understanding of the world. But the second and most important red flag is simply the presence of Fo-Ti in Arey’s supplement.

Fo-Ti, used in traditional Chinese medicine, is reported in China to be the most common cause of liver damage due to the ingestion of an herb. It’s unclear exactly how Fo-Ti causes liver toxicity, although a family of molecules known as anthraquinones are thought to be responsible. Up to one in ten cases seen in the clinic have been fatal or led to an urgent liver transplantation. Because Fo-Ti, like so many herbs thought to have medicinal properties, is sold to help alleviate just about anything, from dizziness to constipation, many people end up taking it for one reason or another. Cases of liver toxicity due to this herb have been reported in many countries, including Australia, Japan, and the Netherlands. There is also a chance Fo-Ti can interact with medications and a non-negligible chance that what you think is Fo-Ti is not actually Fo-Ti, as the scientific literature on the adulteration and contamination of herbal medicines is filled with alarming reports. None of this is reassuring.

We are thus faced with a product that, in my opinion, has not been adequately studied to prove its central claim of slowing down the greying of hair and which is said to contain an herb that has been implicated in many cases of liver toxicity. The argument we are always left with is, “Why don’t you try it and see for yourself?” I’ve been served this argument every time I criticize a questionable health intervention. The problem with the argument is that my own personal experience can be influenced by many factors outside my control. But the problem is made worse in the case of Not Today, Grey. How can you tell that your hair is still turning grey but at a slower pace than it would have otherwise? This is a conundrum that, I believe, can only be resolved by randomly assigning a large group of participants to either taking the supplement or taking a placebo, following them for years, and comparing them. In other words, we need a double-blind, randomized, controlled clinical trial of some magnitude.

For those of us who are not ready to go grey, I am encouraged by the work of scientists who are uncovering what is going on at the cellular and molecular level to slowly turn our hair grey, especially since this work contributes to our general understanding of ageing. But I’m not willing to risk the health of my liver on a supplement supported by a single study in 30 participants. The prospect of liver toxicity alone makes my hair stand up.

Take-home message:
-Scientists do not fully understand why human hair loses its colour as we get older, although it has been hypothesized that pigment-producing cells and their precursors are damaged over time by oxidative stress
-A new supplement, containing vitamins, minerals, and a Chinese herb, is marketed as being able to slow down the greying of the hair based on a single, unpublished study in 30 participants
-The supplement contains an herb called Fo-Ti which has been reported in China as the number one cause of herbal-product-related liver damage

You may have heard of the 50-50-50 rule—that 50% of us will have had 50% of our hair turn grey by the age of 50—but a large study reveals this to be an overestimation, with between 6 and 23% of people sporting a half-and-half by the age of 50. Europeans and their descendants tend to go grey before Asians and Africans, and some people’s hair goes grey prematurely at a much younger age. While scientists can’t agree on a clear age cut-off for what constitutes premature hair greying, they have discovered a number of risk factors for it, which include smoking, certain vitamin deficiencies, and genetics, because premature hair greying can run in families.

But she never thought that it would become a reality. One night, as she was engrossed in a book about ancient spells, Alice stumbled upon a chapter about Chucky, a notorious and malevolent spirit. Intrigued, she decided to read more. The book warned that anyone who uttered Chucky's name would fall victim to his dark spell. Unbeknownst to Alice, she had already spoken Chucky's name aloud. As the words escaped her lips, a shiver ran through her body, and a sinister smile crept across her face. From that moment on, Alice's life took a sinister turn. She began to hear whispers in the shadows, taunting her every move. Objects would move on their own accord, and strange occurrences became a daily ordeal. Her once bright and cheerful home became a place of despair and fear. The walls seemed to close in, the air grew thick with negative energy, and sleep became an elusive dream. Alice tried everything to break free from Chucky's grip. She sought help from mediums, priests, and even tried to perform her own exorcism rituals. But nothing worked. Days turned into weeks, and weeks turned into months, and Alice's spirit grew weaker with each passing day. The dark spell of Chucky had consumed her, leaving her a mere shell of her former self. As she lay in bed one night, with tears streaming down her face, Alice felt a flicker of hope. In a moment of desperation, she called upon the power of love and light to rid herself of Chucky's curse. In that very moment, a wave of warmth washed over her. The whispers in the shadows vanished, and the darkness slowly lifted. Alice knew that she had won the battle against Chucky. Although scarred from the ordeal, Alice emerged stronger than ever. She now cherishes every moment of light and love in her life, knowing that she had conquered the dark spell that Chucky had cast upon her. The story of Alice serves as a cautionary tale, reminding us of the dangers of delving too deep into the supernatural. It is a chilling reminder that there are forces beyond our understanding, waiting to ensnare those who dare to invite them in..

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