Fantastic article. During a 2 month medical school rotation on the Navajo reservation in Shiprock,NM, nearly every adult patient with an illness refused to leave unless they got a prescription for Niripsa. While certainly not a pure placebo, Niripsa (aspirin spelled backwards, ensured a happy patient who would follow all the other directions the doctor ordered.
A form of B12 Deficiency Affecting the Central Nervous System May Be New Autoimmune Disease- B12 deficiency with normal labs caused by antibodies to B12 uptake receptors
For years, giving vitamin B12 shots to people with normal vitamin B12 levels has been considered a “poster child for unscientific medicine.” But a new study shows that the old-time doctors may have been right. And millions of people may be suffering from crippling neurologic problems that may potentially be helped by B12 shots or tablets. Despite totally normal blood levels.
Why?
A new study showed that B12 deficiency in the brain in people with the autoimmune disease lupus was four times as common in those with neurologic and brain symptoms. These people had normal blood vitamin B12 levels but severe deficiency in the brain fluid. It was found that they had an autoimmune molecule that blocked the B12 from getting from the blood into the brain.
These autoantibodies target CD320 — a receptor important in the cellular uptake of B12. While the person’s blood tests are normal, B12 in the patient's brain fluid (CSF) are nearly undetectable.
This is not a rare phenomenon.
6% of the population has these antibodies--so we are unnecessarily contributing to potentially crippling effects from B12 deficiency (despite normal labs) , when they could be easily prevented
This is a nice anecdote, but you have to be careful. I have been pressured to try various kinds of alternative medicine, which was expensive and time-consuming and didn't work. When I researched these things online, and found that there was no evidence that they worked, I felt angry that my time and money was wasted, and lost respect for the physician. I remember telling one doctor to "stop sending me to quacks." Fortunately, my PCP does not do this, so far as I know.
I’m all in on EBM. But I recognize that RCT can only discern average causal effects in select populations. It has less to say on individual, case by case scenarios.
Relieving symptoms is half of the reason why we do this. So if something works for a particular patient, even if we don’t know why, and even if “on average” it shouldn’t, by all means keep going anyway.
What I have always taught is that if a patient complains of something, acknowledge it, touch it (it you can, at least lay hands on the patient and examine), and ask questions. It may be a "nothing", but the fact that a physician has taken the time to listen and touch cures a lot of things.
This is a lovely post! In my 16 years of operating my small Assisted Living home in south FL, I've met a lot of older people. This is very true - they feel quite special because their doctor still makes house calls!
We have predominantly dementia, some mental health issues and the usual hypertension, bowel and bladder irregularities, etc. day to day. Of course, a good number have suffered stroke or cardiac arrests, bypasses, and metabolic disorders. Diabetics are common, and we always improve their condition.
Lifestyle is a huge part of this, but B12 is known to be far less absorbed orally, and it's a very important vitamin. We also use magnesium and there are great flavored powders to mix into tea, aiding hundreds of processes.
Another lady has dry/itchy eyes in the morning... Duh, it's the longest without fluids and she wakes with nocturia. "Drink your tea, sweetheart (herbal, fruity, with leaves from my yard - mango, soursop and stevia) you'll feel better." It works Every Time, but we have also a vial of saline drops which she's become quite dependent on - since seeing how we treat a man with glaucoma with drops. "I'll have what she's having" comes to mind, lol.
That said, we have a lady who's wanted a B12 shot for a while. Our doctor says it's not needed and insurance (Medicare) won't cover it. Then once we got a shot for a different resident, and our doctor (sees her monthly) says it wasn't needed by labs. Finally I asked point-blank of the nurse, who reports giving to several clients monthly with good effect - and the doctor, what's the cost out of pocket? It was $35 - I said I will pay for it myself!
So both ladies feel better and they do have neurological issues which seem to improve in my daily view.
It can't hurt them, the body will discard what it doesn't need - I feel the same about vitamin D which has ample evidence of poor sunlight absorption as we age and with darker skin. We are the ONLY AL facility I've ever known who routinely takes resident Outside Daily. We all need the sunlight, and the plants that grow in our Florida sunshine.
Some of the best things in life are free - and the rest of the best things are Included at Angel House!
Under no circumstances can addressing a nutritional deficiency be considered a placebo treatment! Likewise, causing too much B12 can cause problems.
B12 injection, by definition, cannot be considered a placebo. Missing from this article is whether Dr. Eidus checked Lily's serum B12 levels, and whether she had transfer factor deficiency; both are common in elderly patients. Some brands of B12 injection also contain transfer factor.
It's also possible that her serum levels were low enough to cause symptoms noticeable to her, and the injections had real clinical benefit. It's interesting to note that in Japan, higher lab values are used to define and treat B12 deficiency than in the US. Especially with elderly patients, could we be under-diagnosing this in the US?
All that said, yes, placebo treatments can have real clinical benefit, and there may have been a placebo effect for Lily, with it without B12 deficiency. But still, it's inaccurate to call a B12 injection a placebo.
She had symptoms which could have been considered neuropathy. B12 deficiency and other causes were ruled out. Space constraints limited giving the full story. I guess I should have stated that it was my intent to give it as a placebo mainly because the patient thought it would work
The WHO considers 480 dB/ml to be the bottom of the normal range, and Japan, as I mentioned, targets under 500 for treatment.
So I do wonder how often B12 deficiency in the US is incorrectly "ruled out," through no fault of the doctor, but rather because diagnostic parameters might be wrong.
Of course, the happy ending here is that, whether or not Lily actually had B12 deficiency, you gave her the treatment she needed!
How long have we disregarded the effects of nutritional deficiencies? And how seldom are the elderly on top of leading edge nutrition? This is absolutely spot on!
I think it's less that they've been deliberately disregarded (except perhaps by the companies making medications to address various symptoms without addressing the cause), and more that the nutritional deficiency symptoms simply aren't talked about.
I suppose we could put some blame on med school education (or lack thereof), but some also goes both to the FDA and to whatever US scientists quantified the serum levels for deficiencies.
The FDA sets what used to be called the "minimum daily requirement" and is now called "Daily Value" for some of these nutrients at levels that avoid things like rickets (vitamin D) and scurvy (vitamin C). That's a problem. I think they should set an optimum daily value. I know how bad I felt when I was supposedly "borderline" D-deficient AND B-12-deficient, yet the doctor who reluctantly tested me insisted that my levels weren't low enough to cause symptoms. And yes, I'm sure some perhaps even Dr. Eidus here, would insist that any improvement after taking D3 supplements were only placebo effect.
The good news (from my perspective, at least) is that there are many more studies on nutritional deficiencies than there used to be, so at least some researchers are paying attention and asking questions.
While in dental school in the early 60s, I worked for a time as a medications nurse in a large hospital. Things were quite different back then. Pain meds were q4h and q6h and patients were on a roller coaster. I had one patient, who I think really enjoyed her misery, that was constantly calling for more pain med. The doctor wouldn't up the dose but she was driving me crazy. I came up with the idea of giving her sterile water injections between the real meds. It worked like a charm. She believed she had received pain meds and her pain went away. I have been a real believer in the placebo effect ever since.
Ad a PT and someone who believes the mind is the strongest and best healing organ we have, nothing about the shots surprises me. There is much literature on sham placebo surgeries, ultrasound etc. I hear of stories whereby a patient was told your knees will be gone by 30 and guess what, they show up at 39 and can hardly move (nocebo effect). I wish more orthos would tell patients this injection lasts 4 years and goes everywhere in the body that it is needed. Instead they tell them you can have this every 3-4 months or it takes a week to work if at all. Ugh. Lastly, the piece not addressed (and Lily maybe wouldn't have been open to this ) was addressing the subconscious effects of trauma that she experienced and multigenerationally as a source of the symptoms. When you have subconscious "dis-ease", your body will bring you disease as a manifestation of that. And again, depending on the trauma, it may be too great to face. So we do what we can here to support the person's whole being so the trauma is less and hopefully the symptoms are less. But without supporting her in maybe more than just medical ways, its a challenge without a lot of positive change if at all.
The doctor-patient relationship is the heart of medical care. A good relationship creates patient trust, which drives adherence, stronger placebo effects, and generally better outcomes. Without that trust, the system largely falls apart.
Fantastic article. During a 2 month medical school rotation on the Navajo reservation in Shiprock,NM, nearly every adult patient with an illness refused to leave unless they got a prescription for Niripsa. While certainly not a pure placebo, Niripsa (aspirin spelled backwards, ensured a happy patient who would follow all the other directions the doctor ordered.
Maybe the B12 was NOT a pleacebo.
A form of B12 Deficiency Affecting the Central Nervous System May Be New Autoimmune Disease- B12 deficiency with normal labs caused by antibodies to B12 uptake receptors
https://www.medscape.com/viewarticle/form-b12-deficiency-affecting-central-nervous-system-may-be-2024a1000c5q
https://www.science.org/doi/10.1126/scitranslmed.adl3758
For years, giving vitamin B12 shots to people with normal vitamin B12 levels has been considered a “poster child for unscientific medicine.” But a new study shows that the old-time doctors may have been right. And millions of people may be suffering from crippling neurologic problems that may potentially be helped by B12 shots or tablets. Despite totally normal blood levels.
Why?
A new study showed that B12 deficiency in the brain in people with the autoimmune disease lupus was four times as common in those with neurologic and brain symptoms. These people had normal blood vitamin B12 levels but severe deficiency in the brain fluid. It was found that they had an autoimmune molecule that blocked the B12 from getting from the blood into the brain.
These autoantibodies target CD320 — a receptor important in the cellular uptake of B12. While the person’s blood tests are normal, B12 in the patient's brain fluid (CSF) are nearly undetectable.
This is not a rare phenomenon.
6% of the population has these antibodies--so we are unnecessarily contributing to potentially crippling effects from B12 deficiency (despite normal labs) , when they could be easily prevented
I was just about to post about this, glad you did. Reading through all the comments it appears no one is aware of this important recent discovery.
This is a nice anecdote, but you have to be careful. I have been pressured to try various kinds of alternative medicine, which was expensive and time-consuming and didn't work. When I researched these things online, and found that there was no evidence that they worked, I felt angry that my time and money was wasted, and lost respect for the physician. I remember telling one doctor to "stop sending me to quacks." Fortunately, my PCP does not do this, so far as I know.
I’m all in on EBM. But I recognize that RCT can only discern average causal effects in select populations. It has less to say on individual, case by case scenarios.
Relieving symptoms is half of the reason why we do this. So if something works for a particular patient, even if we don’t know why, and even if “on average” it shouldn’t, by all means keep going anyway.
The late Bill Bengston showed there is a healing intent that may mean placebos are potent medication.
What I have always taught is that if a patient complains of something, acknowledge it, touch it (it you can, at least lay hands on the patient and examine), and ask questions. It may be a "nothing", but the fact that a physician has taken the time to listen and touch cures a lot of things.
Nocebo is absolutely critical too.
https://open.substack.com/pub/sanityunleashed/p/nocebo-effects-during-the-covid-event
This is a lovely post! In my 16 years of operating my small Assisted Living home in south FL, I've met a lot of older people. This is very true - they feel quite special because their doctor still makes house calls!
We have predominantly dementia, some mental health issues and the usual hypertension, bowel and bladder irregularities, etc. day to day. Of course, a good number have suffered stroke or cardiac arrests, bypasses, and metabolic disorders. Diabetics are common, and we always improve their condition.
Lifestyle is a huge part of this, but B12 is known to be far less absorbed orally, and it's a very important vitamin. We also use magnesium and there are great flavored powders to mix into tea, aiding hundreds of processes.
Another lady has dry/itchy eyes in the morning... Duh, it's the longest without fluids and she wakes with nocturia. "Drink your tea, sweetheart (herbal, fruity, with leaves from my yard - mango, soursop and stevia) you'll feel better." It works Every Time, but we have also a vial of saline drops which she's become quite dependent on - since seeing how we treat a man with glaucoma with drops. "I'll have what she's having" comes to mind, lol.
That said, we have a lady who's wanted a B12 shot for a while. Our doctor says it's not needed and insurance (Medicare) won't cover it. Then once we got a shot for a different resident, and our doctor (sees her monthly) says it wasn't needed by labs. Finally I asked point-blank of the nurse, who reports giving to several clients monthly with good effect - and the doctor, what's the cost out of pocket? It was $35 - I said I will pay for it myself!
So both ladies feel better and they do have neurological issues which seem to improve in my daily view.
It can't hurt them, the body will discard what it doesn't need - I feel the same about vitamin D which has ample evidence of poor sunlight absorption as we age and with darker skin. We are the ONLY AL facility I've ever known who routinely takes resident Outside Daily. We all need the sunlight, and the plants that grow in our Florida sunshine.
Some of the best things in life are free - and the rest of the best things are Included at Angel House!
Under no circumstances can addressing a nutritional deficiency be considered a placebo treatment! Likewise, causing too much B12 can cause problems.
B12 injection, by definition, cannot be considered a placebo. Missing from this article is whether Dr. Eidus checked Lily's serum B12 levels, and whether she had transfer factor deficiency; both are common in elderly patients. Some brands of B12 injection also contain transfer factor.
It's also possible that her serum levels were low enough to cause symptoms noticeable to her, and the injections had real clinical benefit. It's interesting to note that in Japan, higher lab values are used to define and treat B12 deficiency than in the US. Especially with elderly patients, could we be under-diagnosing this in the US?
All that said, yes, placebo treatments can have real clinical benefit, and there may have been a placebo effect for Lily, with it without B12 deficiency. But still, it's inaccurate to call a B12 injection a placebo.
Thank you. That's exactly what I was about to write.
Good points
She had symptoms which could have been considered neuropathy. B12 deficiency and other causes were ruled out. Space constraints limited giving the full story. I guess I should have stated that it was my intent to give it as a placebo mainly because the patient thought it would work
Thank you, Dr. Eidus. You might be interested in this article: https://www.nyheadache.com/blog-posts/vitamin-b12-normal-blood-levels-are-often-not-normal
The WHO considers 480 dB/ml to be the bottom of the normal range, and Japan, as I mentioned, targets under 500 for treatment.
So I do wonder how often B12 deficiency in the US is incorrectly "ruled out," through no fault of the doctor, but rather because diagnostic parameters might be wrong.
Of course, the happy ending here is that, whether or not Lily actually had B12 deficiency, you gave her the treatment she needed!
How long have we disregarded the effects of nutritional deficiencies? And how seldom are the elderly on top of leading edge nutrition? This is absolutely spot on!
I think it's less that they've been deliberately disregarded (except perhaps by the companies making medications to address various symptoms without addressing the cause), and more that the nutritional deficiency symptoms simply aren't talked about.
I suppose we could put some blame on med school education (or lack thereof), but some also goes both to the FDA and to whatever US scientists quantified the serum levels for deficiencies.
The FDA sets what used to be called the "minimum daily requirement" and is now called "Daily Value" for some of these nutrients at levels that avoid things like rickets (vitamin D) and scurvy (vitamin C). That's a problem. I think they should set an optimum daily value. I know how bad I felt when I was supposedly "borderline" D-deficient AND B-12-deficient, yet the doctor who reluctantly tested me insisted that my levels weren't low enough to cause symptoms. And yes, I'm sure some perhaps even Dr. Eidus here, would insist that any improvement after taking D3 supplements were only placebo effect.
The good news (from my perspective, at least) is that there are many more studies on nutritional deficiencies than there used to be, so at least some researchers are paying attention and asking questions.
While in dental school in the early 60s, I worked for a time as a medications nurse in a large hospital. Things were quite different back then. Pain meds were q4h and q6h and patients were on a roller coaster. I had one patient, who I think really enjoyed her misery, that was constantly calling for more pain med. The doctor wouldn't up the dose but she was driving me crazy. I came up with the idea of giving her sterile water injections between the real meds. It worked like a charm. She believed she had received pain meds and her pain went away. I have been a real believer in the placebo effect ever since.
Positively Agree!
Loved this. Thank you for sharing. This reminded me of something you would write, Dr. Cifu although I didn’t learn any new words!
Lovely rumination, thank you. For a deeper dive into the wonderful mystery of placebo and its ethics in modern medicine, a podcast/audio: https://researchtranslation.substack.com/p/the-placebo-paradox
Homeopathy.
Ad a PT and someone who believes the mind is the strongest and best healing organ we have, nothing about the shots surprises me. There is much literature on sham placebo surgeries, ultrasound etc. I hear of stories whereby a patient was told your knees will be gone by 30 and guess what, they show up at 39 and can hardly move (nocebo effect). I wish more orthos would tell patients this injection lasts 4 years and goes everywhere in the body that it is needed. Instead they tell them you can have this every 3-4 months or it takes a week to work if at all. Ugh. Lastly, the piece not addressed (and Lily maybe wouldn't have been open to this ) was addressing the subconscious effects of trauma that she experienced and multigenerationally as a source of the symptoms. When you have subconscious "dis-ease", your body will bring you disease as a manifestation of that. And again, depending on the trauma, it may be too great to face. So we do what we can here to support the person's whole being so the trauma is less and hopefully the symptoms are less. But without supporting her in maybe more than just medical ways, its a challenge without a lot of positive change if at all.
Love this!
The doctor-patient relationship is the heart of medical care. A good relationship creates patient trust, which drives adherence, stronger placebo effects, and generally better outcomes. Without that trust, the system largely falls apart.
The power of the therapeutic relationship is also a tool. Seeing and hearing your patient is powerdul!
Agree