MY anxiety is a wild beast. It has destroyed relationships, clawed at my insides until I was sick, left me cowering under blankets, plagued me with panic attacks and tipped me into post-natal depression following the birth of my first son.
I was nervous from the beginning.
As a toddler I saw a neighbour fall into a puddle and was — for years — plagued by thoughts of the “drowning holeâ€. I would dream of it, obsess about it, when I closed my eyes at night I would see it appearing suddenly and unexpectedly outside my house, engulfing my baby brother or unsuspecting parents.
I could not be convinced that I was safe.
In primary school I was obsessed with leprosy. As ridiculous as it now sounds I would lie awake, night after night after night, wondering if tomorrow would be my last day on Earth as I disintegrated due to rapid-onset rotting.
As a teen a phobia of vomiting — something that is far, far more common than you might think — meant I was too scared to eat around other people in case I threw it all back up in front of them.
And as a young adult it manifested as panic attacks.
At 25 I had to move back home with my parents and didn’t leave my room for three months, convinced that I would die if I did.
For more than a decade, I have sought a cure. Some things have helped for a while, others not at all, and always anxiety was there in some way. The eternal feeling something catastrophic was about to happen. I have taken medication — Aropax, Cipramil, Effexor, Zoloft to name but a few — tried Cognitive Behavioural Therapy, hypnosis, exposure therapy, visited psychologists and psychiatrists and naturopaths and herbalists and more.
I’ve doggedly practised yoga, meditated morning and night, exercised feverishly to try and get rid of the adrenalin coursing through my veins.
I’ve sought solace in wine and avoided anxiety-inducing situations to the point of agoraphobia. And, for the last year, my anxiety has edged ever closer to depression, as I berated myself for not being good enough to beat what so many seem to view as a personal failing, something I should be able to control if I just tried hard enough.
Yet today my beast, finally, is a paper tiger, a tiny shadow in the corner of my heart. It wasn’t drugs or therapy or deep-bloody-breathing that finally slayed it though. It was a vitamin.
For years, decades, I was looking outside for the answer, when I should have been looking inside all along. Looking at my genes. Because it turns out I have a genetic mutation on one of my genes, one with the rather apt acronym MTHFR. The result is that my body has trouble processing B-group vitamins.
But here’s the thing: I am far from being alone. The genetic mutation also affects close to one in five people and could be responsible for everything from mood disorder or multiple miscarriages to strokes, cardiovascular disease, diabetes and many other illnesses.
And the good news is that the potential treatment — folinic acid — is cheap, relatively easy to find and side-effect free.
The distinction between folinic acid and the common dietary vitamin, B9 or folic acid, is an important one. Variations in the MTHFR gene mean I am unable to convert folic acid into a form my body can use — folinic acid — easily. That, in turn, can lead to a Pandora’s Box of health problems.
Stirling’s Dr Andrew Owen, that comforting medical mix of compassion and curiosity, has been listening to me bang on about my anxiety for more than 10 years.
I first saw him after 12 months of virtually constant panic attacks had stripped 10kg from my frame, caused relentless insomnia and had driven me home from a life overseas, having left a relationship in ruins and on the edge of a nervous breakdown.
He helped me tone down my more manic side with drugs and psych referrals but anxiety had never entirely left me, ready to rear its ugly head in times of stress or when the kids get sick and I suddenly think that weird rash is smallpox (modern eradication be damned) or in the small hours of the night when the tiniest thing can seem like the gravest catastrophe.
Six months ago he suggested I, along with many of his patients, be tested for a MTHFR variation. Aware of research in the area for the last six or so years and the benefits that had been observed from taking folinic acid, Owen conducted his own specific research before deciding to see if it could help others.
“Like any good doctor I tried it on myself first and quickly became aware of a substantial rise in my energy levels,†he says. “After a few of my patients responded dramatically I thought this could be something to use on those who didn’t respond to SSRIs (a type of antidepressant).â€
But, like so much in medicine, the effects of the treatment aren’t utterly predictable.
“Some people with a double mutation don’t necessarily respond dramatically to folinic acid, which is why I use a methyl B12 in combination as there might turn out to be other pathway disorders,†he says. “I’m treating at least a couple of hundred patients with this now.â€
And those patients don’t only include those with anxiety or depression. The doctor has seen improvements in people with fibromyalgia, migraine and hypertension; kids with ADHD and autism.
And then there is me.
As one of Owen’s first patients to try the treatment, my reaction was a bit of an unknown quantity. “But you had one of the most dramatic improvements,†he says. “I have had two or three others with anxiety have a similar response and a large number have found their anxiety has reduced substantially. But I haven’t been able to predict who will work brilliantly on it until I’ve tried it. I’ve met people with a double copy of the genetic variation who haven’t had much in the way of symptoms. There seems to be a link between personality and genetics.
“But I absolutely think this needs a greater GP awareness. There are a large number of people out there who aren’t aware that they could be feeling better.â€
The link between MTHFR mutations, mood disorders and neurodevelopmental problems is not new information to scientists, even though adoption of testing by the broader medical community appears to be a rarity.
Studies have shown homocysteine levels can predict the length someone might suffer from post-traumatic stress disorder, that B vitamins have been observed to relieve premenstrual anxiety, and that MTHFR variations are associated with major depression, bipolar disorder and schizophrenia.
A study in Northern Ireland found a MTHFR variation was associated with an increased risk of depressive episodes. A 2011 study reported a possible link between a different MTHFR variation and ADHD.
A recent study in Arkansas, published in the journal Molecular Psychiatry, found that a group of children with autism who were treated with folinic acid showed significant improvements in verbal communication, receptive and expressive language, attention and stereotypical behaviour. About one third of treated children demonstrated moderate to much improvement.
Studies that definitively prove a link with anxiety are thinner on the ground.
Trying to find a comprehensive study that looks at the possible link between MTHFR variations and anxiety is tricky, even though its link to other mood disorders is extensively researched.
But if you Google “MTHFR and anxiety†you will find more than 129,000 pages devoted to it — most created by people looking for answers.
That my anxiety has a genetic link is, on reflection, no great surprise to me.
My maternal grandfather had what was then known as a “nervous breakdown†and was prone to bouts of melancholy.
My maternal grandmother would suffer from constant nervous attacks that would leave her feeling “oomiâ€, forcing her to rely heavily on Valium in a time when mental health was neither discussed nor publicly acknowledged.
My mum, who has had her own battles with a kind of social phobia, remembers her own health being constantly checked by her mother. Walking past she would raise a wrist to my mum’s forehead and, at the first hint of illness, Mum would be packed off to bed and checked upon compulsively. I have seen this same behaviour in my treatment of my sons. A temperature can be enough to send me off into wild paroxysms of hysteria, imagining every possible catastrophic outcome befalling my bewildered, if snotty, child.
Truth-be-told, Mum’s side of the family is littered with us crazy types, all of us muddling along as best we can, desperately trying to look normal while we indulge in the various routines, compulsions and obsessions that help us feel like we have some kind of control over our anxiety or depression.
If only I’d known that something as simple — and free of side effects — as B vitamins was a credible option before I spent all my money on enough hand sanitiser to keep all the world’s bacteria at bay. And while better sceptics than me have pointed out that anecdotes are not scientific evidence, allow me to share a local success story or two.
Heathfield mother-of-three Lutske Rayner, 59, had tried to treat her depression with antidepressants for more than 20 years.
“I just generally felt like crap,†she says. “I’d been on medication for many years, felt tired all the time, I was eating well but not losing weight, I had no enthusiasm for life.â€
In May last year her doctor tested her for MTHFR mutations and prescribed folinic acid and B12.
“I felt a change within a month,†she says. “I’m not on antidepressants anymore, I was able to come off my blood-pressure tablets too. I feel like it’s given me a new life and made it a hell of a lot easier to get out of bed.â€
Then we have Barbara Preston.
First diagnosed with an apple-sized brain tumour — a meningioma — at 27, she went on to have two more recurrences, at 33 and 39, resulting in five brain operations over the years.
Now 60 and a writer, she found that her memory and mental clarity had declined sharply over the last year and feared she may have been displaying the early signs of Alzheimer’s disease. She started on folinic acid and B12 five months ago.
“I write poetry and rely on mental clarity but that declined last year,†Preston says. “My memory loss affected everything and I felt depressed. I couldn’t see how it could improve. After starting the treatment I saw an improvement after about a month. I felt more confident and I started writing again after not writing for a year.
“It is one of the most effective treatments I have tried in terms of mental clarity. I’m feeling very positive.â€
So if there is a possibility that these common mental disorders could be improved by the addition of a readily available vitamin, why are more general practitioners not testing their patients?
Dietitian and nutritionist Melissa Adamski is the owner of Nutted Out Nutrition and a nationally-recognised expert in the field of nutritional genomics. Broadly, nutrigenetics looks at how human genetic variation results in distinct nutritional requirements, and how diet and nutrition modulate the expression of genes.
Adamski believes a reluctance on the part of many GPs to invest more time in nutrigenetic testing is because there are no best-practice guidelines for them to look to.
“There is lots of information coming out on genetic variations and how that affects our biochemistry and health. However, there is less information on how to address that with nutrition and other health recommendations,’’ she says.
“A lot of practitioners are quite hesitant in using nutrigenetic tests as they are less clear in what we recommend to the patient. Practitioners are waiting for more robust evidence as there is no ‘one size fits all’ solution.â€
She adds that many people don’t actually want to know what secrets may be hiding in their genes, often because they don’t understand that, while genes can’t be changed, their expression sometimes can.
“We don’t have a lot of best-practice guidelines on how to use genetic information,’’ she says. “Misinformation needs to be cleared up — giving people clear examples of what they can change nutritionally to help them. We need to get away from the thinking that genetic testing will just show what things will definitely happen to them and start to understand that it can start to guide preventive health recommendations and treatment options.â€
While a passionate advocate of the future of personalised medicine and allied health practice — in which nutritional genomics will play an important part — Adamski also encourages people to ensure they are informed before they embark on any genetic testing they may be offered.
“Be very clear on what you want to know through the test. Speak to a genetic counsellor or geneticist if you have questions on serious medical conditions and genetics,’’ she says. “Ask lots of questions of your practitioner.â€
Naturopath Carolyn Ledowsky is the founder of MTHFR Support Australia.
She says there is still not a good understanding of MTHFR mutations and their possible links with anxiety and depression in the medical community. “Most medical professionals will disagree there is a link with anxiety or depression,’’ she says. “But 70 per cent of our MTHFR patients present with anxiety.†Depression is also a very big component she adds, explaining that folate is important to the processes that produce key brain chemicals like serotonin, dopamine and melatonin.
“Most MTHFR patients with anxiety also have decreased B6 and zinc in the body,’’ Ledowsky says. “When this is addressed and B12 and folate levels are restored, anxiety will be decreased by about 80 per cent within three weeks or so.
“This has been life-changing for me too. The genetic route is the key to good health. We can’t do anything about the genes we have but we can change the way they act and the results I’ve seen are nothing short of phenomenal. When you view your family history and your genes, you know you will likely head down the same path unless you change the way the genes behave. This is powerful nutritional medicine at its best.â€
So, with this in mind, what does the future hold for those with dodgy MTHFR?
After all of these studies, its implication in a myriad of devastating diseases and conditions, are we actually any closer to being able to use this knowledge to affect measurable and positive change?
Can it lead to cures? Can we stop multiple miscarriages? Help prevent stroke or heart attack? Bring a child with autism back to his or her parents for good? Can all of this knowledge be converted into effective and life-improving treatment backed by robust scientific studies?
The answer is maybe. Or, more optimistically, probably.
Molecular geneticist Professor Lyn Griffiths, the executive director of the Institute of Health and Biomedical Innovation at Queensland University of Technology, is in late-stage research into the link between MTHFR mutations and migraine, especially migraine with aura.
Aura is usually visual but can also be a sensory, motor or verbal disturbance and is seen in about 20 to 30 per cent of migraine sufferers.
Griffiths is hoping results from Phase 3 studies will replicate what has been found in the previous two — that the C677T mutation occurs more often in people with migraine and migraine with aura and that a combination of B-group vitamins can drop homocysteine and significantly reduce frequency, severity and pain.
“We expect to see a more significant response in people with a double mutation but also a response in those with a single mutation by treating them with a combination of folate, B6 and B12,†she says. “You would need to eat buckets of spinach to get the same effect.â€
If Phase 3 trials bear out earlier studies’ results, Griffiths is hoping this will translate into a treatment that could potentially be available within 12 months.
The reduction of my own migraines has been a happy side effect of treating my anxiety with folinic acid and B12. I have migraine with aura. My most notable attack occurred when I was working at Wendys and had to endure an hour of desperation as a crowd demanded sundaes with Smarties and all I could see was a bunch of flashing squiggly lines while I tried not to spew all over the counter. Since starting folinic acid and B12 six months ago, I have had no migraines. That might not be scientific evidence but it’s good enough for me.
An article in the journal Biology and Medicine last year looked at the clinical implications of MTHFR mutations in disease, and certain cancers in particular. The author reviewed its involvement in migraine and stroke, its role in cardiovascular disease and neural tube defects — common and often covered ground in the world of MTHFR.
He left readers with a final (and hopefully inspiring to medical professionals) thought — that although MTHFR gene mutations and their associated health issues affect “millions of people, sadly this is largely ignored. At present there is a great need for understanding the condition and a greater need for its managementâ€.
Maybe you have this mutation, maybe you don’t — many anxiety and depression sufferers will have developed their conditions for many other reasons that have nothing to do with this gene. There are those who will always do better with more traditional treatments. But then there are the mutants — like me.
I can’t change my genes but I’m willing to explore emerging fields that might offer a way for me to live with them. It’s not a cure. I still have my moments and suspect my anxiety is not only caused by a MTHFR mutation but by a combination of personality, learned behaviours, an obsession with medical-reality TV shows and an incorrigible tendency towards fantastical thinking.
I can still experience anxiety. I still sometimes obsess about whether my kids have some deadly tropical disease. But my everyday life is no longer ruled by that awful creeping sensation that something terrible is about to happen.
Perhaps now those other treatments — the psychs and therapists — would have a better chance of success, with the uncontrollable background anxiety finally silenced. In the words of Popeye — who must have had some kind of MTHFR mutation to explain eating all that vitamin B-rich spinach — “I am what I amâ€.
But I admit I do like this new version a whole lot more.
THE SCIENCE BEHIND IT
I apologise, but things are going to have to get a bit technical for a moment.
Six months ago I discovered my methylenetetrahydrofolate reductase gene, known broadly (and aptly) as MTHFR, is a bit wonky. Specifically, I inherited variations in the MTHFR gene, at the particular locations of C677T and A1298C, predisposing me to high levels of homocysteine.
This is a chemical found in a metabolic cycle called methylation that relies heavily on B-vitamins and plays an important role in, among many other things, mood regulation. MTHFR, when working properly, synthesises folate into a specific form needed to turn toxic metabolite homocysteine into methione, which is essential for cell growth and DNA metabolism.
To bypass this problem, all I need to do is take folinic acid (the bioavailable form of folic acid) and methylcobalamin B12. That’s it.
CSIRO principal research scientist, Professor Michael Fenech — who leads the genome health and nutrigenomics project — first started looking at MTHFR because of the C677T’s association with increases in homocysteine, which has also been linked with an increased risk of DNA damage, cardiovascular disease and Alzheimer’s disease.
Professor Fenech says while thousands of papers have been published globally on the association of MTHFR polymorphisms with the risk of diseases of old age as well as pregnancy complications, having a baby with Down syndrome or with neural tube defects, relatively few papers have been published on the effect of MTHFR variations on many other aspects of health in Australia.
Perhaps I should let him better explain the link between MTHFR and depression and anxiety.
“Problems with folate metabolism have been associated with depression and/or anxiety. This is partly due to inadequate SAMe synthesis. SAMe is required for neurotransmitter synthesis which is important for proper nerve and brain function.
“Common polymorphisms (variants) in MTHFR can reduce its activity and potentially lead to a reduction in SAMe and neurotransmitter synthesis particularly if dietary intake of folate and vitamin B12 are also inadequate.â€
So, basically, because my MTHFR is dodgy I have problems making an amino acid that is really bloody important for lots of things and, consequently, the methylation cycle is impaired, my homocysteine levels rise and neurotransmitter synthesis, among other things, is disrupted.
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