More Serotonin Stuff, Patrick Holford and Depression

April 4, 2008 at 7:47 pm (Bad Science, Patrick Holford, Supplements) (, , , , , , , , , , , , , , , , , )

The media simply don’t run news stories that refer to 5-HTP as being risky, as I’ve written about recently, yet they have always been happy enough to promote (or allow columnists to promote) this substance – often without any caveats. I remember The Guardian’s “Ask Emma” featuring 5-HTP in a column that plugged Patrick Holford’s book Optimum Nutrition for the Mind (ONM) and, given that Patrick himself and other popular nutritionists have penned pieces in several national newspapers, it would be a surprise to me if newspapers other than the Guardian hadn’t featured what would appear to be an incredibly safe wonder drug – depending on who you believe. In fact, it’s so good you can even use 5-HTP as a substitute for sleeping pills. Trust me – I’m a nutritionist:

Serotonin and melatonin help you sleep
[…]Melatonin is an almost identical molecule to serotonin, from which it is made, and both are made from the amino acid tryptophan. Melatonin’s main role in the brain is to regulate the sleep/wake cycle.

Many people, especially women, become serotonin deficient. Without enough serotonin you don’t make enough melatonin, and without melatonin it is difficult to get to sleep and stay asleep. […]

One way to improve matters is to provide more of the building blocks that are used to make serotonin and that means 5HTP (5-hydroxyytryptophan) […]

Another option is to take 5-HTP – the direct precursor of serotonin – which, if you are deficient, will allow you to normalize your levels of both melatonin and serotonin. Supplementing 100mg to 200mg of 5-HTP half an hour before sleep can prove very helpful. […]

There is one caution however. If you are on SSRI anti-depressants which block the recycling of serotonin, and you take large amounts of 5-HTP this could theoretically make too much serotonin. While this hasn’t been reported we don’t recommend combining the two, and you should always consult your doctor if you are taking prescribed medication. [Note: there is no reference to concerns over combining 5-HTP and St John’s Wort, just 5-HTP and Pharmaceuticals]

Food or drugs? The verdict
While prescribed drugs can help you sleep during a short-term crisis, their addictive nature and side effects make them a dangerous option. Combinations of nutrients, herbs and lifestyle changes are likely to be as effective without the downsides. These should be your first resort if you are feeling stressed, anxious or can’t sleep.

This is from an email Holford sent to his mailing list on 2nd March 2006. That’s right – I have two-year-old emails from a media nutritionist in my archive folder. Why? They’re hilarious – that’s why. One of my favourite bits of comedy is this: “I am personally delighted to hear that Government is starting to listen to the logic, science and common sense”. Yeah, Patrick loves logic, science and common-sense. Let’s see how good his logic, science and common-sense are. Patrick Holford and his howlers are all over the web. Anyway, enough of this diversion. What does Patrick think would be helpful for depression?

Well, in his book (ONM) he recommends St John’s Wort 300mg 0.3% hypericin – to be taken 2-6 times daily, making that a total intake of 600-1800mg at a cost of 15p per capsule– which means you could be paying from £2.10 up to £6.30 per week (or £9.10 to £27.30 per month). The NHS charge for a single prescription item is £7.10 and some people can get help with payment or even a free prescription. Holford also recommends 5-HTP at 200-600mg daily – costing 28p for a 100mg pill (to be fair, these particular pills do contain vitamin B6, Zinc, Biotin, Folic acid and Niacin as well which I suppose adds to the cost of the formulation). That’s between £3.92 and £11.76 per week (from £16.99 to £51 per calendar month). The two together could come to as much as £72.30 per month. He also recommends high-dose vitamin and mineral supplements – Folic Acid 1200 microgrammes for those with “chronic or severe depression” along with Vitamin B6 100mg. S-Adenosyl Methionine (SAMe) is also recommended at 200mg per day. SAMe can cost around £30 for thirty 200mg capsules. Even without the high-dose vitamins recommended by Patrick Holford, taking the upper level recommendations for supplementation of St John’s Wort, SAMe and 5-HTP would come to over £100 per month – or £1227.48 for a year’s supply. Crikey. To get example prices, I used Higher Nature for St John’s Wort and 5-HTP as they were listed in the back of one of Patrick Holford’s books as a vitamin supplier. I used the first google result for ‘buy SAMe 200mg’ that gave me a price in £sterling because I couldn’t find SAMe on the Higher Nature online store.

How effective are St John’s Wort or 5-HTP/Tryptophan at combating depression? Well, there’s a Cochrane review of 5-HTP and Tryptophan and also a review of St John’s Wort (both reviews are linked at the bottom of this post). The 5-HTP review states that:

Further studies are needed to evaluate the efficacy and safety of 5-HTP and tryptophan before their widespread use can be recommended. The possible association between these substances and the potentially fatal Eosinophilia-Myalgia Syndrome has not been elucidated. Because alternative antidepresants exist which have been proven to be effective and safe the clinical usefulness of 5-HTP and tryptophan is limited at present.

The St John’s Wort review states that:

Current evidence regarding hypericum extracts is inconsistent and confusing. In patients who meet criteria for major depression, several recent placebo-controlled trials suggest that the tested hypericum extracts have minimal beneficial effects while other trials suggest that hypericum and standard antidepressants have similar beneficial effects. As the preparations available on the market might vary considerably in their pharmaceutical quality, the results of this review apply only to the products tested in the included studies.

These reviews are hardly overwhelmingly positive are they?

Serotonin syndrome could be one potential problem with 5-HTP supplementation: see here or here for a bit more info. Serotonin syndrome could also be a problem if you are taking St John’s Wort: Pubmed has an abstract of a paper that includes this quote: “St John’s wort may cause serotonin syndrome in sensitive patients. In addition, St John’s wort may be associated with hair loss.” Interestingly, the mechanisms of action of St John’s Wort and 5-HTP may be similar to those of SSRIs – “St. John’s wort extract Ze 117 (Hypericum perforatum) inhibits norepinephrine and serotonin uptake into rat brain slices and reduces 3-adrenoceptor numbers on cultured rat brain cells” (SJW on Pubmed) and “releasing of serotonin from synaptic knob can be affected positively by activity of serotonin transporter or by tryptophan* (serotonin precursor) availability.” (From here. I had to link to this page – it had the word ‘knob’ in it.) There are other issues with St John’s Wort – see this paper for some examples, such as the reduction in efficacy of several drug groups. Don’t take St John’s Wort if you are using the pill as your only form of contraceptive. Or if you are taking HIV medication, Warfarin, Ciclosporin, anticonvulsants, digoxin, fluoxetine, SSRI’s or Triptans.

My view of St John’s Wort and 5-HTP is that their efficacy is in doubt; they are associated with not-insignificant safety concerns; and they are relatively expensive. These remedies are touted as being safe and natural. There is a common misapprehension that natural = safe and synthetic = harmful. As far as I know, arsenic is natural. As are snake venom, anthrax, poisonous mushrooms and lead. Just because something is ‘natural’ it isn’t automatically safe – buyer beware.

*Note: 5-HTP and tryptophan are both serotonin precursors and this is how 5-HTP is marketed – as a precursor to serotonin. It actually replaced tryptophan on the shelves of health food stores after the banning of tryptophan due to a possible association with EMS.

Resources: NCCAM, Cochrane review of 5-HTP / Tryptophan, Cochrane review of St John’s Wort.

EDIT 02/02/2010: new post on boosting serotonin.



  1. Dr Aust said,

    Nice post, jdc. It is truly amazing how much of AltMed and paticularly Nutritionism hangs on peoples’ bedrock belief that

    “natural = safe and synthetic = harmful”

  2. PJ said,

    The problem is that the sort of people who believe in the ‘natural=safe’ formulation are, let’s be honest, not open to counterarguments or even reasoning because they suffer from a combination of being a bit dim and extreme cognitive rigidity.

    How anyone can argue that 5HTP or hypericum are better and safer than conventional antidepressant medications I don’t know. Any anyway, I thought antidepressants don’t work, and serotonergic medications cause suicide? These people are incapable of consistent and non-contradictory reasoning it would appear.

  3. jdc325 said,

    Thanks for the comments.

    PJ – you wrote:

    Anyway, I thought antidepressants don’t work, and serotonergic medications cause suicide? These people are incapable of consistent and non-contradictory reasoning it would appear.

    I absoutely agree and this was one of the points I was trying to make. I don’t think I put sufficient emphasis on it (or made the point as well as you did in your comment).

    Dr Aust –
    Yes – it’s pretty much all-pervasive isn’t it? Alt-med is virtually built on the premise that natural = safe and synthetic = harmful. I don’t necessarily endorse all of Bruce Ames’s views, but I think he and Lois Swirsky Gold made some really good points in their “Cancer Prevention and the Environmental Chemical Distraction” essay: the Dose Makes the Poison; Even Rachel Carson was Made of Chemicals; Cellular Defenses Against Chemical Carcinogens Work Against Natural and Synthetic Chemicals (the last one isn’t as catchy, but is well worth quoting).

    It is often assumed that because natural chemicals are part of human evolutionary history, whereas synthetic chemicals are recent, the mechanisms evolved in animals to cope with the toxicity of natural chemicals will fail to protect against synthetic chemicals. This assumption is flawed for several reasons.

    Oops, forgot to link: Ames/Gold PDF

  4. Sue said,

    Very good points all around! Yes, there are too many people who think that supplements alone will fix their depression, AND far too many people place too much emphasis on “natural”. What’s fascinating to me is that even the supplement industry itself acknowledges that;

    a) Exercise, and a well-rounded diet (nutrition & mineral-wise) is of a higher priority than products like St. John’s Wort

    b) There’s more scientific evidence for other compounds, like B vitamins and EPA (a fatty acid in Fish Oil) being more effective than St. John’s Wort or 5-HTP

    c) Seeing a mental professional, who can prescribe antidepressants if necessary

    Yes, it’s a great thing that people are taking more responsibility for their own care, and doing research into alternatives — but that research should be a bit more complete, don’t you think? Patient, heal thyself – but under a Dr.’s supervision!

  5. jdc325 said,

    Thanks for your comments Sue. I think I would broadly agree with your points a) and c) – but I am not too sure about b). The page you linked to does claim that there is “reliable and relatively consistent scientific data showing a substantial health benefit” for B Vitamins and Iron – but the information in brackets after each nutrient seems to indicate that the health benefits are being claimed for B Vitamin and Iron deficiency, rather than for depression. I.e., if you suffer from depression as a result of deficiency in one of these nutrients then you may benefit from Folic Acid or Iron supplementation. Of course, if people follow the advice in point a) and have a varied diet then they shouldn’t need supplements at all.

    The site you linked to also claimed that “natural interventions [vitamins, herbs] are usually best geared to endogenous depression”, but this does not seem to be supported by evidence – I tried searching Pubmed for “endogenous depression” and vitamins or herbs and didn’t turn up an awful lot.

  6. Evidencebasedeating said,

    Evidence, Holford style (anecdote approach)


    great article, btw

  7. jdc325 said,

    Hello EvidenceBasedEating and thank you for your kind words. Interesting PDF too – I hadn’t previously been aware of that particular side-effect 5-HTP.

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