Jacob Schor, ND

I’ve been taking capsules of curcumin, a concentrate of the Indian spice turmeric, for so many years now that I must pause to search my memory for a way to calculate just how long.  I started after reading a 2001 paper from UCLA researcher Sally Frautschy suggesting curcumin might be useful in treating Alzheimer’s disease as it appeared to dissolve amyloid clumps in the brain.¹   This was back when amyloid deposits were still considered the cause of Alzheimer’s disease.  Back then I wasn’t worried about Alzheimer’s but was quite aware that amyloid deposits were to blame for a worsening debility affecting my vocal cords.  It was more a hunch to take curcumin than a theory and it seems to have been a lucky hunch as nearly three decades later, although I’ve not experienced a cure, my condition, though worsening steadily, has progressed at a snail’s pace.  I’ve been lucky beyond belief.

Was this disease stabilization, my imagination or some placebo response?  It could be but if it is, then I’m not alone.  Terry Golombick down in Australia had reported in 2015 that a patient of hers with the same rare condition that beset me had responded to curcumin and in personal communications has confirmed that she’s seen other patients with a similar slowing of disease progression as I have experienced.²

Over the years I have paid attention to the evolution of curcumin extracts that are utilized in clinical practice.  Curcumin is a challenge to use in humans as it doesn’t seem to want to be absorbed from the digestive tract into the blood.  If it doesn’t get into the blood, how can it help?  Then there are the breakdown products and what biological impact they might have (see my article on vanilla and these pharmacokinetics³).  This all gets complicated.  The bottom line though is that moving curcumin from a capsule into the blood and to the cells we hope to influence isn’t easy.  Clever chemists and manufacturers have come up with a variety of ways, and products that promise to provide better performance.  My long-time readers will recall that for years I have relied on Meriva, an Italian brand of curcumin that uses phosphatidyl choline to create nanoencapsulations of the curcumin particles to enhance absorption.

I recently attended a naturopathic specialty conference in Seattle, Washington and one of the sponsoring vendors gave me samples of a new curcumin product his company is selling.  He described this new product as ‘amorphous’ rather than crystalline, as if that would mean anything to me.  I found such a term a bit too vague intellectually and my requests for clarification proved futile.  Despite my intellectual dissatisfaction, I came home with samples of their newly improved amorphous curcuminoid material which I took daily for a week.

Curcumin is well known to have an anti-inflammatory effect.  It reduces generalized feeling of aches and pains, what I might privately refer to as Advil deficiency syndrome.  I know when I’ve run out of curcumin because a few days later I start rummaging for said OTC medication.  Within a day of trying this amorphous version of curcumin, I was thinking that indeed it does work better; good news regarding effectiveness, bad news for our personal finances as it is more expensive than Meriva.

How does one make the decision to spend more money on something the seller describes as amorphous without a hint of irony?

Part of my problem has been that while I was experimenting with this new amorphous curcumin, the New York Times published an essay by Ted Kaptchuk.  Kaptchuk is the professor of medicine at Harvard Medical School, who “has been a leading figure in placebo studies for the past 30 years.” Perhaps, the leading figure.

At one point, some years ago, Dr. Kaptchuk was best known as the author of a 1983 book, The Web That Has No Weaver that Amazon still describes as “… the classic, comprehensive guide to the theory and practice of Chinese alternative medicine. This accessible and invaluable resource has earned its place as the foremost authority in synthesizing Western and Eastern healing practices.”

Even though Kaptchuk is not a medical doctor, he has had a respectable career in medicine.  He received a B.A. in East Asian Studies from Columbia University in 1968 and graduated with a degree in Chinese medicine from the Macao Institute of Chinese Medicine (Macao, China) in 1975.  He was recruited as researcher at Beth Israel Deaconess Medical Center in 1990 and became associate director of the Center for Alternative Medicine Research and Education at Beth Israel Deaconess Medical Center, also in Boston.  In 2011, he became Director of the Harvard Program in Placebo Studies and the Therapeutic Encounter at Beth Israel Deaconess. He has been a faculty member at Harvard Medical School since 1998, a professor of medicine since 2013, and professor of global health and social medicine since 2015.⁴  He is the acknowledged expert on placebo effects. 

Was the amorphous benefit I thought I felt from the new curcumin ‘real’ or merely placebo effect?

Using placebos in medical practice, that is providing patients with inert substances while pretending they are receiving an active treatment, has long been an accepted part of medical practice but in recent years has become ethically questionable. The concept of patient autonomy arose during the mid-1900s as an important tenet in medical ethics:

“Unlike their medical forebears, physicians today are expected to furnish patients with adequate information about diagnoses, prognoses and treatments. Against these dicta there has been ongoing debate over whether placebos pose a threat to patient autonomy. A key premise underlying medical ethics discussion is the notion that the placebo effect necessitates patient deception.”⁵

How does one prescribe a placebo without practicing deception?  Though there are papers in the medical journals that debate the difference between deception and lying, it is hard to get around the idea that placebo use requires one or both to work and our modern sensibility insists that doctors should be honest practitioners.

There is little doubt that well administered placebos often relieve pain and discomfort, that’s not the issue.  In fact, in a 2020 review paper published in the British Medical Journal, Kaptchuk wrote that in data gathered from 140,000 patients suffering from various chronic pain conditions, placebo responses accounted for 50 to 75% of the benefits provided by drug treatments for pain.  Similar percentages are seen for relief of cancer-related fatigue and menopausal hot flashes.⁶

The problem remains that giving a placebo is inherently a dishonest act and for doctors and scientists, deceiving patients is ethically frowned upon to the umpteenth degree.  Even if they help relieve pain.  Something of a quandary for an ethical doctor.⁵

Yet this quandary doesn’t stop doctors from using placebos. In 2008 more than half of internists and rheumatologists in the US admitted to using placebos, that is “a medication such as vitamins or analgesics that would have no effect on the illness but were prescribed for their psychological value.”⁷ In the UK placebo use is even higher: In a 2013 survey, 97% of primary care doctors admitted to using a placebo at least once in their career and 77% say they prescribe a placebo at least once a week.⁸

Some years back, in 2010, Kaptchuk turned placebo research and even our concept of what a placebo is, upside down by doing something bizarre; he conducted a clinical trial with “open label placebos.”  Both the doctors and the patients receiving the placebos, knew that they were using a placebo. Nothing was hidden… there was no deceit involved.  Patients with diagnosed irritable bowel syndrome (IBS) (n=80) were divided into two groups, half of whom received inert sugar pills and the other half nothing.  Those who received the sugar pill experienced global symptom improvement by day 11 and by the end of the trial at day 21, had experienced significant reductions in symptom severity and relief of symptoms.  Although it did not reach significance even their quality of life was trending in the right direction, towards better.⁹  In a recently published and very similar study, improvements in IBS symptoms were also seen in children (n=30).¹⁰

At the time many thought these results were a fluke.   As Kaptchuk writes in his NY Times piece, “Currently, more than a dozen randomized trials demonstrate that open-placebo treatment can reduce symptoms in many illnesses with primarily self- reported symptoms such as chronic low back pain, migraine, knee pain and more. These findings suggest that patients do not have to believe, expect or have faith in placebos to elicit placebo effects.”¹¹

If this doesn’t strike you as weird and unexpected, you should back up a paragraph or two and reread what I just wrote.

At this point there is enough evidence to support this open-labeled placebo effect that we should admit that it probably does occur.  The first questions we ask ourselves of course is how or why?

Kaptchuk suggests:

… that for certain illnesses in which the brain amplifies symptoms, engaging in a healing drama can nudge the brain to diminish the volume or false alarm of what’s called central sensitization — when the nervous system overemphasizes or amplifies perceptions of discomfort. This mostly involves nonconscious brain processes that scientists call Bayesian brain, which describes how the brain modulates symptoms. The intensification and the relief of symptoms use the same neural pathways. Considerable evidence also shows that placebos, even when patients know they are taking them, trigger the release of neurotransmitters like endorphins and cannabinoids and engage specific regions of the brain to offer relief. Basically, the body has an internal pharmacy that relieves symptoms.”  A placebo, even one that a patient knows is a placebo may be surprisingly effective in treating chronic pain conditions.¹²

This theory that suggests the brain or nervous system has a volume control, what Kaptchuk calls ‘central sensitization’ that either amplifies or turns down the intensity of sensations will make sense to anyone who has gone through a tick season in Maine. Once you have found a single tick crawling anywhere on your skin, or worse burrowing into your skin, for days if not weeks afterwards, one clearly knows that their ’central sensitization’ has changed:  one feels hypersensitive to any sensation of touch on the skin.  If a random hair is pushed askew, is moved ever so slightly, you are immediately aware and need to investigate the cause to be certain it isn’t another tick.

All of this brings me back to wondering about my new purchase of amorphous curcumin… do I really feel better when taking it or has my Bayesian brain simply turned down my pain amplification system in response to what might be a placebo?  Apparently even if I knew it was a placebo, it might still allow me to feel better.  I haven’t a clue and will put off deciding at least until I finish taking the pills in the bottle that I’ve already paid for. 

Assuming everyone is honest (that includes researchers, drug manufacturers, supplement vendors and medical practitioners), how do we know if something helps on its own or is just triggering a placebo effect?  I start taking an amorphous substance in capsules and start feeling better.  Is my perceived pain relief resulting from the stuff inside the capsules or is it just placebo effect?  Even if I’m told and know that there is nothing useful inside the capsules, I could still, quite plausibly, feel significantly better because that Bayesian brain has been kicked into action by an open label placebo and making a miscalculation, that still leads to an anti-inflammatory effect.  It doesn’t seem that making up placebo pills to take—even if I make them myself—will answer this question as in theory my homemade, open-label placebo pills, that I know are inert, may still provide pain relief. 

The extra hassle and expense of performing randomized placebo-controlled trials has long been deemed worthwhile as such studies allow us to calculate whether the active ‘drug’ is more effective than a placebo.   In clinical practice I’ve heard that some practitioners will initially start by prescribing a placebo to patients before switching to an active treatment as a method to determine if the treatment works better than placebo. Perhaps this procedure works, but at this point I am hesitant to assume anything when it comes to placebo effect, at least until the process is better understood.

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References

1. Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci. 2001 Nov 1;21(21):8370-7.
2. Golombick T, Diamond TH, Manoharan A, Ramakrishna R. Stabilisation of Laryngeal AL Amyloidosis with Long Term Curcumin Therapy. Case Rep Hematol. 2015;2015:910528. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496470/pdf/CRIHEM2015-910528.pdf
3. https://www.naturalmedicinejournal.com/blog/vanillin-found-jugs-ancient-tomb-leads-questions-its-use-inflammation
4. https://www.tedkaptchuk.com/ assessed 10/28/2023
5. Blease C, Colloca L, Kaptchuk TJ. Are Open-Label Placebos Ethical? Informed Consent and Ethical Equivocations. Bioethics. 2016 Jul; 30(6):407-14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4893896/pdf/nihms764629.pdf
6. Kaptchuk TJ, Hemond CC, Miller FG. Placebos in chronic pain: evidence. 10.1136/bmj.m1668 PMID: 32690477. https://www.bmj.com/content/370/bmj.m1668
7. Tilburt JC, Emanuel EJ, Kaptchuk TJ, Curlin FA, Miller FG. Prescribing “placebo treatments”: results of national survey of US internists and rheumatologists. BMJ. 2008 Oct 23;337:a1938.
8. Howick J, Bishop FL, Heneghan C, et al. Placebo use in the United Kingdom: results from a national survey of primary care practitioners. PLoS One. 2013;8(3):e58247.
9. Kaptchuk TJ, Friedlander E, Kelley JM, et al. Placebos without deception: a randomized controlled trial in irritable bowel syndrome. PLoS One. 2010 Dec 22;5(12):e15591 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008733/pdf/pone.0015591.pdf
10. Nurko S, Saps M, Kossowsky J, Zion SR et al. Effect of Open-label Placebo on Children and Adolescents With Functional Abdominal Pain or Irritable Bowel Syndrome: A Randomized Clinical Trial. JAMA Pediatr. 2022 Apr 1;176(4):349-356.
11. Kaptchuk TJ. NY Times. Oct 10, 2023. Assessed 10/28.2023.
12. Kaptchuk TJ, Hemond CC, Miller FG. Placebos in chronic pain: evidence, theory, ethics, and use in clinical practice. BMJ. 2020 Jul 20;370:m1668.

Published June 15, 2024

About the Author 

Jacob Schor, ND, now retired, had a general practice with a focus on naturopathic oncology in Denver, Colorado. He served as Abstract & Commentary Editor for the Natural Medicine Journal for several years (https://www.naturalmedicinejournal.com/) and posts blog articles on natural therapies,  nutrition, and cancer (https://drjacobschor.wordpress.com/). He was a board member of CoAND and past president of OncANP, and is someone who is happier outdoors than inside.