Let me tell you a story about a nausea medication.

If you’ve ever been pregnant or known someone who was, you’re probably aware of morning sickness.
There’s also a morning sickness on steroids called hyperemesis gravidarum (HG) than can last *past* giving birth.
(Thread)

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The problem with HG is the pregnant person needs to divert about 1000 calories a day so the cluster of cells can keep dividing into interesting shapes, and they need to increase their blood volume so they can handle the little xenomorph’s circulation & waste disposal needs.

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Which is REALLY FUCKING HARD WHEN WATER MAKES YOU PROJECTILE VOMIT LIKE A TEENAGER AFTER TEQUILA.

HG can be life-threatening if the pregnant person gets dehydrated or their electrolytes drop, and it’s definitely pregnancy threatening.

(Plus dental & esophageal erosion)

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Nausea meds shouldn’t be that hard, but they’re complicated when someone is growing a little xenomorph that’s incredibly sensitive to drugs.

Turns out? Pregnancy nausea may exist in part to protect the parent and spawn from molecules that will fuck up development.

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We know this because one of the very first truly effective drugs for pregnancy related nausea caused major neuromuscular & skeletal anomalies.
That was thalidomide, and is the reason we now test drugs more thoroughly, yet hardly any of them are available to pregnant people.

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So the nausea problem remained.

There had been folk remedies for centuries, with varying effectiveness. But in the early 50s (before the thalidomide problem became obvious), the early antihistamines showed a LOT of promise for managing HG.

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Especially when combined with a common, cheap, safe vitamin. It makes sense — the first gen antihistamines are REALLY good at getting the parasympathetic nervous system to chill the fuck out. (Para = smooth muscles, not under voluntary control. In this case, digestive.)

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(They’re also sleep aids.)
Human bodies have a high tolerance for that specific type of antihistamine & can clear it without doing lasting damage. We’re kinda sort of built around that histamine-antihistamine biochemistry; our bodies tolerate it, even when growing xenomorphs.
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So... back in the 50s, Benedictin was a VERY early, effective HG med - Benedictin. It was a combination of the first gen antihistamine doxylamine, the anticolergenic/anti-spasmodic (still used to treat IBS) dicyclomine, and the vitamin, pyridoxine (B6).

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More than a generation of pregnant people took it with good results — less HG, no clear developmental anomalies.
Then in the 70s, the FDA checked the combination & realized that dicyclomine did at best nothing. (Too complex for 280.)
Benedictin was withdrawn from the market.
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OBs were comfortable prescribing doxylamine & pyridoxine, and kept doing so for the next 30 years. Since they were both generic, the cost to stave off HG was usually well under $10/month.
Both were well tolerated; by the 2000s, there was +40 years of history proving safety.
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It’s an old antihistamine and a vitamin. Easy dosages. Cheap.

This combination should be too cheap and too unprofitable for Big Pharma to waste any money on.
The target market only needs it for under a year, often only a couple months.

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It comes with a massive liability risk, because grief and anger don’t bring our best selves out. There’s always a litigator willing to take advantage, and thanks to thalidomide, any drug taken in pregnancy will always be suspected.

A risk assessment says not worth it.

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And yet? That incredibly cheap, practically ancient first gen antihistamine and the vitamin?

Retails for around $230 for a 30 day supply.
It’s not a generic. It went back on the market in 2013 as a patented medication, Bonjesta (aka Diclegis).

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Bonjesta is 20mg of each, in one pill.
Doxylamine alone? It’s sold over the counter as Unisom sleep tabs. 25mg per tablet. Runs about $7 for a box of ~30.
25 mg Pyridoxine (B6) tablets? $2-3 for a 30 day supply by scrip.
(+/- 5mg is fine in this equation.)

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Which doesn’t stop Duchesnay (Bonjesta/Diclegis’ manufacturer) from raking in $230 per patient per month for as long as the hyperemesis lasts.
Insurance companies usually include it on the formulary, because Bonjesta has a 60+ year known safe history.
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(Classed as a tier 3 or 4 brand name drug, though)

If insurance won’t pay for Bonjesta, they will often pay for Diclegis, which is chemically identical to Bonjesta, but comes in a 10mg/10mg format, and retails for about $70 for 30 tablets, or $125 for 60 tablets a month.

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So, how is a drug that’s itself old enough for Medicare still on patent & still commanding name brand prices?
Good question.
There’s a little bit of time release technology, but not much (and it doesn’t change the effectiveness of the combination).
The big issue? The safety.
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Basically: Duchesnay did the paperwork to get it back on the market. With such a long history, doing the research was cheap, and it’s a needed drug. A safe antiemetic makes pregnancy safer and easier for everyone.
And the combo works, so it was worth Duchesnay’s money.

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Honestly? It’s worth having on the market, as a standard first line treatment, in a single pill that is a simple dosage.
(I swear this is not me defending pharma as an industry; it’s an acknowledgement that meds are difficult for people in distress, so simplification is GOOD.)
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Which brings me to supplements and “doctor’s formulations” sold by supplement companies.
What Duchesnay & Bonjesta prove is that a safe, effective combination of cheap chemicals will be brought to market IF (big if) they work.
No matter how old or forgotten.

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Let’s say you’re a biochemist/research pharmacologist with a track record for developing safe, effective drugs to fill a hole in the market. You’ve made your own company and other companies (and yourself) an obscene amount of money.

And you come to them with another one.
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You’ve got prizes and awards and you’re a rainmaker.
This formula uses several known to be safe chemicals rather than a unique molecule (so more like Bonjesta than Lipitor). Which means research costs will be low. It fills a needed niche in the market. It’s a long term drug.
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There will be no problem patenting it. Any drug can be made time release or faster acting. Research costs will not be out of scope.
Why won’t a company sell it? They will only refuse it... if it doesn’t work.
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Same with competitors — a competitor loves nothing more than to poach a rainmaker pharmacologist from a rival.
If Pfizer doesn’t want the drug, Eli Lily will be DELIGHTED to take it.

If it works.
But if the research is sketchy or can’t be replicated? They, too, will pass.
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It doesn’t matter if the components are cheap. Better if they are!
Nor if they’re available OTC. Again, better if they are, because that’s a green light on safety.
Nor if this combo is available in 10 supplements.
1 pill convenience always sells.
It simply has to work.

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If it doesn’t work? Well, there’s a Nobel laureate hawking a formula for Herbalife.

If it did, as Bonjesta proves, Pfizer would have kept it, and made another billion dollar fortune. It would not be sold through a pyramid/multi-level marketing scheme based in the Caymans.
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A medication to prevent or reduce the risk and severity of heart disease would be a money spinner for any pharmaceutical company.

Seriously, that’s what statins and blood pressure meds do, and they end up being life-long drugs. Pharmas would LOVE this maintenance drug.
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Even if it only reduced the frequency of angina by 5% or reduced heart attacks by 2%, it would be in high demand, and it would be of benefit.
Pharma management aren’t skeptics — they believe their OWN hype.

If pharmas couldn’t find that level of efficacy? It doesn’t work.

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(Hell, the first generation of SSRIs were only 1-2% more effective than placebo, and a hell of a lot of the control group testers were convinced they were getting the drug, not the sugar tablet. Pharmas truly don’t object to narrow efficacy margins.)
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Same for any formula that looked like an effective weight loss aid. Same for “male performance enhancement.” Hell, same for “strong nails and hair.”

If Pharma could make any of these work, they would. They’d be ecstatic. There is a market and it’s worth the cost.
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If something is sold as a supplement, it’s not because Big Pharma Won’t Make Money On It, So Won’t Bother. (That’s marketing.)

Bonjesta proves Pharma can make money on ANYTHING that works. It’s on the supplement market because the science failed, & supplements don’t give a damn.

The supplement market is completely unregulated.
ALL they are required to do is print a disclaimer on the bottle (This statement has not been evaluated by the Food & Drug Administration. This product is not intended to...)
AND not make *SPECIFIC* curative claims.
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They can say “supports a healthy immune system” or “keeps blood vessels toned.”
(Really? Do veins post selfies on Instagram as proof?)

They can’t say “prevents cancer” or “cures arteriosclerosis.”

(And most supplements companies skate as close to that line as they can.)

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About every 3 years, a research org or major media outlet will send samples of the most popular supplements for analysis.
Every time, at least half come back contaminated or simply not what’s on the label.
Every time. Here, have links.
35/ https://www.nytimes.com/2013/11/05/science/herbal-supplements-are-often-not-what-they-seem.html

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https://www.nytimes.com/2015/02/07/opinion/herbal-supplements-without-herbs.html

https://sciencebasedmedicine.org/fda-warns-companies-selling-illegal-hangover-remedies/

https://www.consumerreports.org/vitamins-supplements/the-truth-about-black-cohosh-supplements-for-menopause/

https://www.consumerreports.org/dietary-supplements/fda-finds-hidden-drugs-in-weight-loss-sexual-enhancement-dietary-supplements-sold-on-amazon-ebay/

https://www.consumerreports.org/dietary-supplements/illegal-stimulants-in-bitter-orange-weight-loss-supplements/

https://sciencebasedmedicine.org/commercial-deception-undeclared-drugs-in-herbs-and-other-dietary-supplements/

https://www.consumerreports.org/vitamins-supplements/lead-poisoning-from-dietary-supplements/

https://www.washingtonpost.com/health/brain-boosting-supplements-may-have-high-doses-of-unapproved-rx-medications/2020/11/20/d998b686-17dd-11eb-befb-8864259bd2d8_story.html

Often, the analysis comes back with contaminants like lead.
Or sildenafil (viagra) in “herbal viagra”.
Most herbals aren’t the plants they claim, especially North America native wild plants. (There’s not enough wild to support 10 bottles of capsules at all 6800 GNC shops.)
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(Even if there was, how do you know the conditions a “wild” plant grew in? If you’ve grown hot peppers, you know this concept — a thirsty, over-warm plant produces much hotter peppers than one kept wet and cool. The weather can make weak or WAY TOO STRONG herbals.)
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And getting the wrong plant can be lethal. Don’t confuse white boneset (folk remedy for dengue fever, not fractures) with white snakeroot, for example. Same family, they look a lot alike, but the latter will kill you dead. Painfully. Slowly. (See: milk sickness. It’s tragic.)
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Truly: if you cook, you already know this — the difference between dried oregano and dried basil is not obvious. Or ground cumin & cinnamon. Or turmeric and curry.

It’s even less obvious when it’s a powdered plant in a capsule.
And there’s no real testing.
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The FDA has almost no control over supplements & herbals, thanks to Orrin Hatch.
They DO control over-the-counter meds (which is why there’s an Excedrin recall on) & prescription meds.

But that capsule? Could be filled with flour or milk powder or chalk or powdered parsley.
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You’re reliant on what the company tells you, because most of us don’t have access to mass spectrometers (quiet, Phil) or gas chromatographs to do the analysis ourselves.

And often, the company is reliant on whatever bulk manufacturer _they_ contract with.
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In case you’ve already forgotten — we’ve been through this with pet food in the recent past, in 2007-08.
Chinese suppliers bulked out corn gluten, wheat gluten, rice protein and other vegetable protein isolates with melamine powder.
It caused kidney failure and death.
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It also happened with Chinese baby formula in 2008-2009.
Melamine is a tasteless, odorless powder that’s high in nitrogen.

Food quality assays often use nitrogen as a proxy for protein... so melamine powder was a cheap way to raise the score. Too bad it’s poisonous.

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What about Customs?
What about them?
25,000 20-foot containers come through the Port of Los Angeles alone every single day.
There are only 45,600 Customs agents & officers in the whole national bureaucracy.
You tell me if they’re testing everything that comes through.

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Everyone in that production chain has an incentive to lie about their product and substitute a cheaper, hopefully harmless, look-alike.

Around 40% of the buyers will SWEAR they felt something, because about 40% of people are deeply susceptible to the placebo effect.

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(It’s fine. ~40% of people think prayer helps, too. Everyone is welcome to their magical thinking, we just don’t make public policy based on it, because your magic & mine are opinions, not testable facts.)
Another 20-30% don’t know if a supplement helps, but will gamble.

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The rest who try a thing? Well, the company still sold a $30 or $80 bottle, at least once.
Not bad for (usually) $1-2 worth of powder & capsules.
Do enough of that and your CEO’s getting a beach house in the Caymans AND the Seychelles.

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This isn’t me letting Pharma off the hook.
Pharma is greedy.
They’re shady AF.
They’ll steal your socks without taking off your shoes, then sell your socks back to you at a markup.
They are rat bastards.
But they have a watchdog. Often toothless, usually slow, but a watchdog.
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There’s NOBODY watching supplements until AFTER they’ve done damage. If then. And usually not until there’s a body count.

Except the NYTimes, sometimes. And Consumer Reports, amongst all the other things they have to test. And a few state Attorneys General.

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Remember the NYAG assay: 50% were not what was on the bottle.

Imagine if every birth control pill ever had a 50% chance of being fake.
Or if 1 in 20 blood pressure tablets would spike your pressure instead of lowering it.

Would you ever put even one in your mouth?

~end