The problem for nutriceuticals

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You wrote to me to suggest that supplements work…. but this highlights a problem for nutriceutical studies.

There is no patent protection to be had and so pharmaceutical companies are not willing to spend big bucks to do a study where anyone can come along and sell the product without any outlay for drug development.

So someone says let’s do a prevention study with supplement X….we hear about it all the time, but it is a small study done over a short time because it lacks financing. The trials give an iffy result but is an heroic failure and this gets done over and over again as there is enough info to allow a positive spin to be made.

But this study is different it is massive and done over 5 years and a prevention study to look at supplementation to stop autoimmunity. What does it find?

Well the paraphrased conclusions are “Vitamin D supplementation for five years, with or without omega 3 fatty acids, reduced autoimmune disease…..Both treatment arms showed larger effects than the reference arm (vitamin D placebo and omega 3 fatty acid placebo)”.

The media then say “Vitamin D supplements with or without Omega-3s decreased risk of autoimmune diseases”

Great we say and I have to say wow this study has over 25,000 participants over 5 years which is a long time to study if vitaminD and omega 3 supplementation stop autoimmunity. Now the glass half-empty person say “Has the magical statistical significance of P<0.05 been reached to suggest that results are not due to chance?” The answer should be…….NO. But that is not the interpretation given.

The answer is too tight to call, so I would say do it again or carry on to ten years as there was no difference for the first three years Maybe 5 years is not long enough . Maybe the dose was wrong, and I suspect the study population was wrong as this was done in adults and I am guessing looking at chldren may have been more fritful

But will they do it again?. I suspect not. People will look at the take home message that supplementation works after all P=O.O5 and the confidence interval does not cross one it is 0.99 after all. But Omega-3 (fish oils) fails to meet the statistical hurdle and theorectically should “bite the dust” as a single therapy in adults. I will keep taking my supplements in the belief they are useful but incremental

But, you have a trial of 25,000 people over 5 years and you got a p=0.05 with vitamin D supplementation, but if this happened for a pharmaceutical you probably would not be making it a best seller. Now a glass half-full person will take the positives from this, but it should warn you that if neutriceuticals work they are probably going to have an incremental effect.

My mantra: Low-side effect, expect low efficacy

Now this is not a treatment study, it is a prevention study and also it is not an MS study. The authors need to be congratulated but it shows the prevention road is not going to be quick and it is not going to be easy.

What if you looked at vitamin D and EBV inhibition?

Hahn et al. Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial

Objective To investigate whether vitamin D and marine derived long chain omega 3 fatty acids reduce autoimmune disease risk. Design Vitamin D and omega 3 trial (VITAL), a nationwide, randomized, double blind, placebo controlled trial with a two-by-two factorial design. Participants 25 871 participants, consisting of 12 786 men ≥50 years and 13 085 women ≥55 years at enrollment. Interventions Vitamin D (2000 IU/day) or matched placebo, and omega 3 fatty acids (1000 mg/day) or matched placebo. Participants self-reported all incident autoimmune diseases from baseline to a median of 5.3 years of follow-up; these diseases were confirmed by extensive medical record review. Cox proportional hazard models were used to test the effects of vitamin D and omega 3 fatty acids on autoimmune disease incidence. Main outcome measures The primary endpoint was all incident autoimmune diseases confirmed by medical record review: rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, psoriasis, and all others. Results 25 871 participants were enrolled and followed for a median of 5.3 years. 18 046 self-identified as non-Hispanic white, 5106 as black, and 2152 as other racial and ethnic groups. The mean age was 67.1 years. For the vitamin D arm, 123 participants in the treatment group and 155 in the placebo group had a confirmed autoimmune disease (hazard ratio 0.78, 95% confidence interval 0.61 to 0.99, P=0.05). In the omega 3 fatty acids arm, 130 participants in the treatment group and 148 in the placebo group had a confirmed autoimmune disease (0.85, 0.67 to 1.08, P=0.19). Compared with the reference arm (vitamin D placebo and omega 3 fatty acid placebo; 88 with confirmed autoimmune disease), 63 participants who received vitamin D and omega 3 fatty acids (0.69, 0.49 to 0.96), 60 who received only vitamin D (0.68, 0.48 to 0.94), and 67 who received only omega 3 fatty acids (0.74, 0.54 to 1.03) had confirmed autoimmune disease.

Conclusions Vitamin D supplementation for five years, with or without omega 3 fatty acids, reduced autoimmune disease by 22%, while omega 3 fatty acid supplementation with or without vitamin D reduced the autoimmune disease rate by 15% (not statistically significant). Both treatment arms showed larger effects than the reference arm (vitamin D placebo and omega 3 fatty acid placebo).

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MouseDoctor

8 comments

  • Presumably this was a US study. It refers to ‘non hispanic white’. In Europe we wouldn’t have a separate category for the Spanish (although certain diseases are more common in ‘Mediterranean’ population, eg Sickle cell). I intend to keep taking my Vit D.

    • Harvard. I am experimenting with avoiding links to the original papers as it brings in too much heat from irate reseaearchers if they don#t like what is written.

  • In terms of drugs. Maybe ‘My mantra: Low-side effect, expect low efficacy’ as your body is thrown out and something unnatural is occurring in the body.

    However things that are part of your natural lifestyle may not have big side effects as your body is familiar with them and doesn’t react abnormally.

    For example – look at EBV, ok not a drug, may have no side effects but it can cause MS

    Low Vitamin D levels, no side effects but if it’s Vit D or low UVB light either way it’s linked to increased MS

    Smoking, no short side short/medium side effects, however accelerates MS progression and can cause other illnesses

    Exercise, no side effects but is nuroprotective and can preserve BVL

    The list goes on, powerfull drugs obviously have effects and can damage your body. But maybe natural molecules arnt as severe on your system as your body can naturally process them 🤷‍♂️ But equally essential

    • Agreed you make good points….but I am talking about immunomodulating effects and if they are having strong inhbitory effects to inhibit disease then they are probably having strong inhibtory effects on infection protection as the methods of targeting are non-selective and the same…. so if neutraceutic has minimal impact on infection control, I doubt the effect on MS response is massive either. You talk about smoking, vitamin D but whilst the influences are present as you say, they are still small effects (risk is often not even doubled)…….Exercise no side effects try….hip replacement:-).
      Vitamin D, UVB may be linked to vitamin D, but if the effect is when you are in your mother’s uterus (e.g. month of birth effect( doing a study on vitamin D enhancement 30 years after birth is not going to make an impact. I am not saying these aspects have no effect but the question is how do you show the effects, use trials of 50,000 people and for 10 years, but how many can you do.

      • Yes I know what your saying, I totally agree with you. The effects individually maybe to small for individual supplements or changes to lifestyle. These are never going to be picked up in trials to have a significant benefits but accumulatively they might. To hard to prove though.

        I suppose as long as there not shown to make MS worse then it comes down to the individual to make the choices, like Vitamin D supplementation, omega 3s, ALA etc. Youl never know if it has an effect over the course of your life. But i suppose you’ve got to take a chance.

        At the moment MS needs a sledge hammer, to treat. It may not be the case in time to come.

  • On this theme, I would love to see a study on MS and lysine supplementation. Some people swear by it for HHV 1,2 and 3 (shingles, not chickenpox), so it is likely to have an inhibitory effect on HHV4 (EBV) too. The evidence that EBV causes MS is now clear to anybody who has their eyes open and can solve the following equation (1+1=?). There is biological plausibility in the form of interplay between the epigenetic enzyme lysine (K)-specific demethylase 2B and EBV infection (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580945/) and https://www.sciencedirect.com/science/article/pii/S004268220291562X.

  • I think one of the problems with these studies is the expect a linear response to dose and assume people don’t have other sources. This is reasonable in drugs but not food, and something created by sun exposure.

    As a controlled endocrine system ( 25(OH)D/1,25(OH)D in the blood) I would only expect to see an effect of vitamin d on health in those who are deficient. I would not expect any short term effects on those that are sufficient. Any long term effects are because you never become deficient. If they wish to see a pharmaceutical effect they are going to have to go close to toxic levels. Sufficient is above where the parathyroid hormones plateau and below about half of where toxicity sets in.

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