…Brain regeneration after depression, brain degeneration causes bipolar depression, regenerating the brain naturally by boosting brain derived neurotrophic factor (BDNF)…
… Stress causes depression and bipolar…
 

-Beyond Neurotransmitters-
-How to Regenertate your Broken Brain-

PLEASE FORGIVE THE UNFINISHED STATE OF THIS PAGE IT IS STILL UNDER CONSTRUCTION AND THE HIGHLIGHTED TEXT IS NOT PROOFREAD, I’M SHARING THE WORK I’VE DONE SO FAR 7TH OF APRIL [#16]
 
© www.PeterSmithUK.com 2014 (updated April 2015)

You’ll be familiar with the model that mental health problems can be caused by neurotransmitter deficiencies, however you may not have heard of the new model that mental health problems are caused by a deficiency of BDNF the brains protective growth protein. 

BDNF protects brain cells from damage and stimulates them to make new connections and new research has found low levels of BDNF leads to loss of function in key areas of the brain involved in:
  • depression,
  • bipolar syndrome,
  • OCD,
  • cognitive decline/Alzheimer’s,
  • and possibly chronic fatigue syndrome
People with major depression, bipolar depression and OCD show shrinkage in key parts of the brain involved in maintaining mental health and the new thinking is these problems may not be so much lack of neurotransmitters in the synapses or pathways that carry the neurotransmitters but an actual lack of synapses to carry the neurotransmitters in the first place. 
 
The good news is you can regrow and regenerate your synapses and brain pathways by increasing the production of the brains natural growth factor called BDNF (brain derived neurotrophic factor). 

Below I’m going to show you how to use natural remedies to boost BDNF and stimulate regeneration of your brain.
 
In addition to the above conditions boosting BDNF may assist the recovery from brain injury or stroke and recovery form drug withdrawal.

In terms of mental illness stimulating brain regeneration goes beyond simply propping up inadequate neurotransmitters and I believe is one of the most exciting breakthroughs in in mental illness in decades.  I’ve used my BDNF boosting protocol on myself and in my practice with great results.
 

So What is BDNF ?

  • BDNF is a protein naturally produced in our brains, it’s a desirable thing you want more of it.
  • BDNF protects brain cells from shrinkage and death from stress, toxins free radicals etc it prolongs the life of brain cells.
  • Not only does BDNF protects brain cells from becoming damaged but also acts like a fertiliser or growth stimulant; it stimulates nerve cells to sprout new connections with their neighbours, these connections are the synapses it’s where neurotransmitters are produced and transmitted.
  • BDNF also stimulates the growth of completely new brain cells something that used to be thought impossible.
  • BDNF levels are suppressed by the stress hormone cortisol.
 
I’ll go into it in more detail later but in brief the new BDNF research suggests that depression for example is not a deficit of serotonin within the synapses it’s a deficit of the number of synapses that transmit serotonin. BDNF literally stimulates our brain cells to grow new synapses and boosting BDNF production offers a completely new approach to treating mental illness that goes beyond boosting deficient neurotransmitters. Furthermore as I’ll explain later on believe the way stress depresses BDNF damages the physical brain seems to unite psychotherapy/psychology and physical brain treatments for the first time.
 
You can think of BDNF like a rooting-fertiliser that stimulates plant roots to grow and branch out, BDNF is miracle-grow for the brain. 
 

How can you get more BDNF in our Brain?

We can increase BDNF levels naturally with specific cocktail supplements, fasting, specific exercises and relaxation response brain training exercises. Below I’ll show you my BDNF treatment protocol to regenerate your brain.
 

The BDNF Model of Mental Illness

When our body has a stress response we release the hormone cortisol which is diminishes the of protective BDNF and increase the level of inflammation in the brain; the new understanding is that the combination of reduced BDNF levels combined with increased inflammation results in damage and loss of function in the parts of the brain that control our mood and happiness, this diminished function then causes a depresses mood and mental health problems. The same phenomenon is thought to operate in bipolar and possibly OCD. 
 
When our brain produces stress response whatever the cause it sends the stress signal to the hypothalamus which tells the pituitary to tell the adrenal glands to release the stress hormone cortisol the hypothalamus-pituitary-adrenal pathway is called the HPA-axis and studies have shown that people with depression and bipolar have hyper-activity in the HPA-axis, it’s unclear why this occurs but the effect of overactivity in the HPA-axis is damage to key structures in the brain involved in maintaining mental health.
Numerous studies have observed that the brains of people with chronic depression, bipolar syndrome, OCD and possibly other anxiety disorders:-
 
  • have an overactive HPA-axis causing them to overproduce stress responses and cortisol,
  • have diminished levels of BDNF,
  • have degeneration of neural pathways in key areas that affect mood and behaviour. It looks like this degeneration is the result of increased levels of inflammation and low levels of BDNF [i] [ii].
The figure on the left shows the key structures of the brain that show signs of shrinkage in the brains of people with chronic depression and bipolar syndrome.

Reduced BDNF levels of BDNF and increased inflammation can cause either loss of the branch like connections between nerve cells called dendrites which diminishes the number of synaptic connections between brain cells forming neural networks or it can cause actual death of the brain cells.
 
When I first heard about chronic depression and bipolar syndrome (which I have) causing shrinkage and loss of brain function I was quite upset about it, my initial understanding was that the damage involved death of the cells and permanent loss of function however I was pleased to discover a lot of new research shows that this is not the case and that the cells are in fact still alive and can regenerate. It seems just their dendritic branches have shrunk, like a tree that’s had its branches trimmed by a tree surgeon, it’s still very much alive and the branches can regrow.
 
Scans of the brains of people with depression and bipolar syndrome before and after receiving treatment show significant regrowth of dendrites and synapses (see figure).

In the figure opposite you can see how the image in the middle of a depressed brain cell has a decreased number of dendrites(the branches that extend from one nerve cell to its neighbours), in the top of the picture you can clearly see a diminished number of synapses (each of the little buds would have a synaptic connection to another cell, not all the connections are shown to simplify the picture), on the right you can see how treatment has stimulated regrowth and increased the number of dendrites and synapses. The same effect has been observed in brains of people with bipolar syndrome and as soon as I saw this I decided I was going to move the health of my own brain from the situation depicted in the middle image to the one on the right; I began to research how can raise BDNF levels and regenerate my brain. I started working on my BDNF increasing protocol in 2013, I applied it first to myself then introduced it to my practice in 2014 and straightaway it seemed to be changing lives; and perfectly well aware my personal experiences and observations in my practice do not constitute a double-blind placebo-controlled crossover clinical trial, if you’d like to invest a couple hundred thousand pounds conducting such a trial I’ll share everything I learnt with you for free; but in the meantime neither my patients or I have the time to wait, we want to improve our lives and live well with our mental illness straightaway, we want effective practical solutions that don’t produce toxic side-effects will make us feel unwell and as long as what we’re trying is safe to take and it’s a safe period in our life to be experimenting we can conduct our own personal treatment trials to look for better solutions. 

To formulate my BDNF increasing protocol is sourced each of the individual components (turmeric, lithium, calendula, zinc et. al.) I sourced from the scientific literature, my contribution was to try putting all the BDNF increasing techniques together at the same time applying the relaxation response brain training techniques have been developing for the past couple of decades, and also either at the same time or beforehand paving the way for increased BDNF levels to regrow and regenerate the brain by targeting and treating anything that could get in the way such as high blood sugar imbalances, an unhealthy inflammation promoting diet, food sensitivities particularly gluten from grains, and unhealthy intestinal flora et al. So each of the individual components I recommend to boost BDNF has been scientifically researched however the combined protocol I propose is experimental, if you try this protocol please share your experiences on my forum, Facebook or Twitter accounts which I be starting in summer 2015.

Which specific regions of the brain become damaged and the extent of the damage caused by a high stress/low BDNF environment will vary in different people resulting in different conditions; for example if there’s loss of serotonin or dopamine/norepinephrine carrying synapses in key pathways in the limbic system involved in feelings of pleasure and happiness your capacity for generating feelings of happiness can become all but switched off. As an analogy imagine the thousands of individual neurones that are bundled together to form a major pathway giving you the capacity to generate healthy happy emotions like it was a bundle of individual wires forming a thick cable under the street, when fully operational the cable can supply high-speed broadband internet to the whole street, however if rats chew through many of the individual wires it could reduce the carrying capacity of the cable so that now it can only deliver low-speed dial-up internet; in a simplistic way you can imagine damaged neurological pathways mean your capacity for generating and conveying happiness has been reduced from high-speed broadband to dial-up. If an engineer was called out to fix the problem when they discovered the cause of the problem was rats partially chewing through the cable what a good engineer would do is firstly exterminate the rats, secondly repair the cable and finally bolster up the protection around the cable to prevent further rat damage. What a good engineer wouldnot do is just boost the current through the cable; in the brain when we experience this type of loss of function rather than just going straight into the synapses with drugs and trying to boost the level of neurotransmitters in the remaining synapses I believe a superior approach should start with eliminating the source of the damage (principally overactivity in the HPA-axis), then stimulate the damaged neurological fibres/pathways to repair themselves and also include treatments to protect the brain from the ravages of excessive stress responses in the future.


As already mentioned excessive stress responses can be a major source of harmful chronic inflammation that damages neuronal networks however there are several other sources of chronic inflammation in the brain including: exposure to free radicals (from smoking, poor diet particularly rich in fried foods and exposure to environmental toxins), food allergies and sensitivities (gluten should be particularly singled out in this regard), high blood sugar, unhealthy intestines with a leaky intestinal wall that permits half-digested food to enter the bloodstream and provoke an inflammatory immune response, if a leaky gut wall is also coupled with a leaky blood brain barrier so that half-digested food molecules can not only enter the bloodstream across the blood-brain barrier to enter the brain this can cause very harmful persistent inflammation; each of these sources of inflammation could potentially be capable of preventing the brain regenerating protocol from working and so must eliminate them all.  
 
The way overactivity in the HPA-axis produces inflammation is one of the actions of the stress hormone cortisol is to aggressively activate our immune system including immune cells in our brain that then release inflammation promoting chemicals into our brain called cytokines. A short-term elevation in cytokine levels to fight off the cold for a few days is not a problem but when cytokine levels remain persistently elevated it wears down and neural networks to the point where we can break down for no apparent reason seemingly unrelated to external sources of stress or a neural pathways may be pushed to the verge of breaking down and with a little extra external sources of stress we break down.
 
You can think of the cytokines as the rats that chew through the cables in the analogy.
 
Chronic stress responses are doubly bad, firstly they produce chronic inflammatory cytokines levels that damage the brain and secondly they decrease the production of BDNF the very thing we need more of to protect ourselves from the chronic inflammation in the first place.
 
I’m not going give any references because the science is changing so rapidly but it now seems that there are also genetic differences in the way peoples brains respond to stress, in some people chronic stress responses reduce BDNF levels resulting mental health problems whereas other people may possess brains that are more resilient to elevated stress levels.
It may not be great to have a brain that “breaks down” due to chronic stress but if that’s what you’ve got it’s good to know because there are things you can do to stop it calling you health problems in the future; this is the type of thing that holistic functional medicine does really well, and mainstream medicine doesn’t. Elsewhere on my site I discuss how to permanently hardwired new ways of dealing with stress responses seethe stress solution.
 
As I’ve already mentioned above studies have shown that people chronic depression and bipolar syndrome overproduce stress responses compared to people without mental illness, hypothetically it’s possible that having a brain that over produces stress responses and having a brain that’s easily damaged by stress hormones are two independent things i.e. a person could have a brain that over produces stress responses but is quite resilient to the effects, alternatively a person could have a brain that doesn’t excessively produce stress responses but nevertheless is highly vulnerable to damage from stress, or you could have a highly stressed and highly vulnerable brain.

Another phenomenon is that we can become completely habituated to chronic stress responses so that we no longer feel we’re stressed, I often meet such people in my practice, they have long since lost any sensations or awareness that they are heavily over-producing stress responses which can make it hard for them to believe this issue relates to their condition, but exaggerated stress responses are an integral part of the physiology that causes these problems and changing this physiology is an essential part of your recovery. You have to do the relaxation response brain training exercise for the brain regenerating protocol to work, not doing so is likely to lead to failure, it’s a dealbreaker.
 

Depression and BDNF

As explained above people with depression and bipolar syndrome overproduce stress responses whether they know it or not, the stress hormone cortisol reduces the level of protective BDNF and at the same time increases the level of damaging inflammation, this combination causes loss of healthy function in the parts of the brain involved in feelings of happiness and depression.
 
Interestingly antidepressant drugs have been shown to increase BDNF levels and the BDNF hypothesis of depression suggests an alternative explanation of how these drugs work. The new thinking is that antidepressant drugs treat depression by stimulating regeneration[iii] rather than the traditional theory that they work because they boost neurotransmitter levels.
 
Actually the moral that antidepressants work because they increase BDNF explains how antidepressants workbetter than the theory that they increase neurotransmitters. There’s a well-known flaw in the neurotransmitter model which is that neurotransmitter levels rise rapidly within the next day but antidepressants generally take one and a half to three weeks before they begin to relieve symptoms; if the principal therapeutic action of antidepressants is to increase BDNF levels however that fits what we observe because it takes some time for increased BDNF levels to regenerate brain cells sufficiently to affect symptoms and the timelag of one and a half to three weeks fits perfectly. 
In reality antidepressants drugs probably work by both mechanisms of boosting neurotransmitters and brain regeneration.
 
An obvious question at this point is if antidepressant drugs boost BDNF levels and regenerate the brain why don’t I recommend them in my brain regenerating protocol and the answer is side-effects. For example many people experience a loss of libido when they take antidepressant drugs however they may experience a healthy return of libido when they take natural antidepressant remedies and then there’s the weight gain side effect which the natural remedies don’t cause; I could go on but I think with erectile dysfunction and weight gain I’ve probably made my point to both men and women.
 
I only work with non-toxic side-effect free remedies derived from naturally occurring substances, I understand that not all naturally occurring substances are non-toxic but herbal and nutritional compounds are part of the body’s normal economy, we ingested and evolved with these substances, our digestive system, hormonal system, metabolic pathways and the livers detoxifying enzymes are used to handling these naturally occurring compounds.
 
Having said that if antidepressants were used for a limited period of time as part of a focused anti-inflammatory and brain regenerating protocol which included dietary change, psychotherapy and relaxation response brain training I could see a place for them, but sadly this is not generally the way they are used in mainstream medical practice.
Chronic depression can take a toll on the health of the brain, many of my patients complain of diminished mental and cognitive abilities after a bout of depression, these problems often only become apparent once the depression breaks. People can find it harder to concentrate, study and perform the mental tasks they used to be able to do, all of which can make it hard for them to resume their life; if this happens to you try my brain regenerating protocol in combination with huperzine A, alpha GPC, citicholine and DMAE.
 

Bipolar and BDNF

There has been some contradictory research finding increased levels of serum BDNF at least in periods of bipolar mania [iv], however I do not think that we should be concerned about small number of studies showing elevated BDNF levels because the consensus is studies finds low levels of BDNF in people with bipolar syndrome[v] [vi] [vii] [viii] [ix]. There is also robust evidence that the HPA axis is hyperactive in people with bipolar syndrome [x] [xi] so if you have bipolar syndrome you should train your brain to compensate for this with relaxation response brain training.
 
I suppose hypothetically you might be concerned that boosting BDNF in the middle of a hyper-manic episode could grow and develop the (dopaminergic pathways of the brain that are already hyperactive however another concern is we want to protect the brain from the damage inflicted on it during this stressful time. Another way of looking at this is that in general boosting BDNF tend to have an antidepressant effect and remember that treatments have the potential to intensify and precipitate mania.
 
If you currently have bipolar mania, bipolar mixed state or ultra-rapid cycling as I’ve said elsewhere the place to start is always getting the mania under control first, with aggressive treatment you can typically bring mania under control quite quickly then as soon as you’ve set up preventative anti-mania measures such as sleeping in total darkness you could start boosting BDNF. Initially you could begin by only taking the Lithium orotate (if you’re not already taking it) and high doses of supplemental zinc, these remedies not only boost BDNF but also help stabilise mood and encourage sleep which is a great antidote to bipolar mania. 
 
There’s a good reason why you would want to undergo a brain regeneration protocol if you have bipolar syndrome and that is that the long-term combination of high inflammation from a hyperactive HPA-axis and low BDNF levels with repeated bouts of mania and depression takes a big toll on the health of the bipolar brain scans of which show shrinkage in both the grey matter and white matter, interestingly BDNF levels improve following successful treatment of bipolar syndrome with pharmaceutical lithium carbonates or valproate [xii].
 
I believe boosting BDNF is not only a good thing to do for people with bipolar syndrome because it regenerates damage inflicted on brain but also because it treats and improves the long-term stability of the condition itself. Before I performed my own BDNF boosting protocol I used to have to take both Rhodiola and tyrosine on a daily basis to boost my dopamine levels and manage my bipolar depression, the problem with boosting dopamine is that it can quite easily flip you up into mania. My treatment regime would involve a juggling act of applying the ‘gas’ when I was depressed, lifting my foot off the gas and applying the anti-mania breaks when I started moving in a manic direction; however since performing the BDNF boosting protocol are no longer need to take Rhodiola and rarely tyrosine.
 

My Personal BDNF Versus Bipolar Story

During my late 30s and into my 40s my bipolar syndrome was becoming increasingly intense with stronger and more frequent mania, in response I learned to be more proficient at manage it with a regime of lifting myself out of depression or switching off manias as they arose, eventually I learned how to keep my condition completely under control and remain essentially well as long as I maintained a very hands-on regime of controlling my dopamine levels like driving a car you apply the gas or restricted gas and apply the brakes. My rapid cycling bipolar however was ever present and stronger than it had ever been, I could feel it more or less constantly trying to destabilise me and at least once a day a week I would need to quickly alter my prescription to stop things getting out of control. About every 2 months or so it would break free like a horse escaping its stable and I would have to jump on it by taking up to 50 pills a day for a few days which would quickly bring it back under control. To an outsider this may seem like a lot of work but untreated bipolar syndrome can be a life-threatening nightmare so I was just really happy to have solutions that worked.
 
Eventually further research led me to the new concept of regenerating damaged neurological pathways by boosting BDNF. I put together a basic BDNF boosting protocol and applied it to myself twice, initially for 3 months then for a 2nd 6 week treatment and the effects have been tremendous:
 
The first thing I noticed was just I spontaneously stopped taking Rhodiola which was a remedy I absolutely could not do without, whenever I discontinued it within 5 days I would rapidly start descending into a low grade depression with a loss of motivation, pleasure and tiredness strong enough to restrict my activities; I’d been dependent on Rhodiola for 3 or 4 years and just halfway through my first brain regenerating treatment I could stop taking it.
Next I spontaneously stopped taking tryptophan and I’d been dependent on that for about 15 years to top up my serotonin levels. I only had to take 3-4 days a week so it wasn’t much of a hardship but whenever I stopped taking I would begin to become depressed with painful, antsy feelings.
I used to have to take tyrosine first thing every morning 7 days a week, now however I take it only once or twice. 
 
Not only was I able to give up these antidepressant remedies but there was also a noticeable improvement in my mood, I felt more upbeat and positive but not in a manic way which has a distinctive speedy quality.
 
We are far from fully understand what goes on in the brain so I’m only speculating about what caused these benefits but I believe the reason I was able to give up the above remedies is because I’ve grown new synapses, so I no longer have to take tryptophan to top the level of serotonin in my synapses because I now have more serotonin carrying synapses, going back to the analogy I used above previously have upgraded my serotonin pathways from low speed dial-up to broadband. The same thing appears to have happened to my dopamine pathways enabling me to give up Rhodiola and significantly reduce my reliance on tyrosine. Whether or not this explanation is correct is less important than the fact that worked.  
 
Since taking the BDNF boosting protocol I now go for a week or week and a half without being able to feel the bipolar syndrome at all compared to the past where even when I had it under control I could still feel it there ever present in the background. Despite now having days or weeks when I feel totally cured I know from bitter experience that I still have bipolar syndrome and maintain continue treatment.
 
I think the BDNF boosting protocol also may have reduced my rapid cycling although I mainly attributed this to trying the new approach of taking a low dose of lithium orotate on a daily basis, either way I’m happy to report that I’ve had a two thirds reduction (from 6 times a year to twice a year) in my rapid cycling, diagnostically this means I no longer have rapid cycling.
 
In addition to the above improvements in my bipolar syndrome there was another very impressive effect on my brain. The five-year depression I had during my early 40s had damaged my brain, I noticed a decline in my facial recognition and hearing in particular indicating degeneration within my brain :-( however after performing my BDNF brain regenerating protocol not only did these things returned to where they had been before that long depression but my hearing is actually better now than it was in my 20s! The way I know my hearing is better now than it was in my 20s is that there are many songs that I’ve been listening to on the radio since the 1980s and I’ve never been able to understand the lyrics but it didn’t matter I just liked the sound, after doing the BDNF boosting protocol I started to understand the lyrics to many songs and unfortunately in many cases this ruined the song for me, in this regard ignorance was bliss. I haven’t upgraded my hi-fi since 1997 so it must be because I regenerated the parts involved in hearing and upgraded my brain.
 
Performing the BDNF boosting protocol hasn’t cured my bipolar syndrome but it has made it easier to manage and I now have the best mental health I’ve ever had. It’s also helping my patients, I hope it helps you.
 

Anxiety and BDNF

From the research it is not clear yet how much BDNF is involved in anxiety disorders[xiii], or even if it involved at all. One confusing issue was that results varied depending on whether or not the study measured BDNF levels in the blood plasma or blood serum. OCD was the exception and it looks certain that low levels of BDNF are involved in OCD.
 
Vigourous exercise reversed low levels of BDNF in people with panic disorders and improved symptoms[xiv], not all exercises raise BDNF to the extent, below I’ll tell you the most effective form of exercise.
 
Even if the research is unclear about BDNFs involvement in anxiety disorders I still recommend regime to improve the fundamental health of the brain.
 

Other conditions involving BDNF

It’s not my area of speciality but low levels of BDNF have been observed in schizophrenia and eating disorders implying it may play a role.
 

Suicide: Low BDNF Levels Can Kill You

Low levels of BDNF have been found to be associated with suicidal behaviour [xv] and improving your BDNF levels could save your life.
 
Mental illness kills people, people with mental illness that commit suicide don’t choose to take their own life the illness killed them; a mistake many people make is thinking that mental illness especially depression is just in the mind, but it isn’t it’s a physical illness in the brain in which a person’s mind and behaviour are altered and hijacked by the chemical and physiological imbalances in the brain.
 
If you are suicidal right now understand that you have a chemical imbalance in your brain altering your psychology, that you have a life threatening illness that’s trying to kill you and if you can hold on while you treat the imbalance in your brain the painful psychology driving you suicidal thinking can disappear, the illness can alter your thinking in a way that tells you that nothing can help change the reality of how you feel but your perception of reality is altered, that’s the illness talking and it gives you a distorted view of your world. 
 
As someone that’s lived with bipolar syndrome since the 70s I know this from personal experience my illness has nearly killed me many times. When you are in remission suicidal feelings completely go away and boosting BDNF levels together with hardwiring into the brain healthier ways of managing stress responses is the most effective way I’ve discovered so far of maintaining long-term remission.
 

For the Best Outcome Use a Mind & Body Approach
On their own neither Psychological or Chemical treatments may be enough resolve a mental health problem and prevent it recurring.

Something I really like about the BDNF hypothesis of depression is that for the first time there seemed to be a good model that can bring together the psychologists/psychotherapists on the one hand and the brain/neuro scientists on the other. Both sides can agree that it is chronic stress responses that cause depression by damaging the brain. The BDNF hypothesis seems to finally explain how talking therapies can be effective even for serious mental illness, by reducing psychological trauma they can reduce the level of stress responses which increases BDNF levels and brain repair.
 
(Insert diagram): Stressful Thinking and Psychology à Chronic Stress Responses à Decreased BDNF Levels àDecreased Brain Cell Protection and Repair à Lesions/Breaks in Neuronal Pathways in the Limbic (emotional) Centre of the Brain à Depression
 
This may seem to imply that psychotherapy treatments are superior to chemical therapies because they treat the origin of the problem, unfortunately however all too often psychotherapy on its own is not enough to cure real mental health problems because there are real structural and chemical conditions in the brains of people with mental illness and although psychotherapy may remove original triggers of ongoing stress responses this alone may not increase BDNF levels enough to regenerate the brain without additional physical assistance of chemical remedies.
The new science of BDNF shows us that depression and bipolar syndrome are in fact brain illnesses but that they may have their origin in psychological trauma, however there are of course many people that go through extremely stressful and traumatic experiences without developing mental health problems so it’s the combination of stress responses and brain vulnerable to break down and not just the presence of stress per se.
 
I believe the BDNF hypothesis of mental illness should refocus both psychotherapists and psychiatrists, I believe it tells the psychotherapists that when they are treating real mental illness the goal of the therapy is to unearth and resolve psychological trauma that’s causing excessive stress responses, low BDNF levels, brain damage and the mental illness; and it should tell psychiatrists that unless if you only treat a person with chemical approaches and they don’t make any fundamental shifts in their psychology and/or the way they deal with stress they are likely to repeatedly relapse, what psychiatrists call the revolving door syndrome. 
 
I believe strongly in the healing powers of psychotherapy even just as little as a dozen CBT sessions should be considered as an essential component of the treatment for depression. Imagine repairing the brain by replenishing BDNF with drugs or natural remedies but leaving in place unchanged the type of stressful psychology and thinking that depleted your BDNF levels and damaged your brain in the first place, what will probably happen is gradually over time continued stress responses will recreate the problem. Even if the stressful psychology that depleted BDNF levels was more external in origin rather than deeply ingrained in the your psychology from childhood and traumatic experience, the fact that external stress resulted in brain damage and depression implies you have the brain that can break down under stress and you would be well advised take steps to prevent this happening again in the future; with a bit of work over a three-month period you could install new ‘software’ in your psychology with psychotherapy and ‘hardwire’ the ability to switch off stress responses by performing my relaxation response brain training protocol. 
 
If you are having psychotherapy as soon as or whenever you feel you make a significant breakthrough in your therapy you could take BDNF boosting protocol below to enhance your transformation.
 

Cognitive Decline Alzheimer’s and BDNF

My expertise lies in mental illness and I have not attempted to treat Alzheimer’s or cognitive decline however in researching the role of BDNF and neuroplasticity for mental health problems I constantly found scientific literature alluding to their significant role in Alzheimer’s and cognitive decline, BDNF protects brain cells from degeneration and increases the brain’s capacity to regenerate and make new connections. In the past I deliberately avoided commenting on Alzheimer’s and cognitive decline because I didn’t feel there was anything useful or practical to say either in terms of treatment or prevention apart from intermittent fasting and not overeating is the best prevention. In 2014 this situation changed when for the first time cognitive decline was reversed in humans [i] by a Dr Bredesen using what mainstream medicine describes as a novel approach but interestingly for me the approach was individualised functional medicine which is what I do. I now think finally there are some currently available techniques we that may help at least the early stages of cognitive decline and Alzheimer’s. I would suggest combining the techniques used by Dr Bredesen with my BDNF boosting protocols to increase neuroplasticity. At the moment I’m engaged in writing up my therapeutic methods for mental health problems however at some point in the future (2016) I’ll be putting up pages on nondrug approaches to cognitive decline.
 


[i] Reversal of cognitive decline: A novel therapeutic program Dale E. Bredesen,  Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, University of California, Los Angeles, CA 90095; 2 Buck Institute for Research on Aging, Novato, CA 94945.
 

BDNFs other roles in the Body

BDNF performs many other functions in the body outside the brain. It is involved in stabilising blood sugar and insulin metabolism, preventing insulin resistance and type II diabetes, IBS, healing the intestines and intestinal movement. 
See Blood Sugar and Mental Health.
 

The New Science of Neuroplasticity

The ability of the brain to regrow and regenerate is called neuroplasticity and below I’m going to show you how to increase your neuroplasticity using natural remedies.
Neurones come in different shapes and sizes
it’s all about number of dendrites and synaptic connections…
 
We could for example meditate on happiness, love, detached mindfulness, forgiveness
Although this chapter is about how to boost BDNF to repair damaged brain pathways you can also use the BDNF boosting protocol any time you want to learn or develop a new mental ability to accelerate the process of the brain making new connections, if you do try using it with learning languages, improving maths abilities etc. let me know he get on. For mental health problems what I’m proposing is that let’s say you had depression in the past and you’ve already done the BDNF protocol once along with taken remedies to rebalance your neurotransmitters and you’ll now feeling much better but you still have for example low self-esteem you could then redo the BDNF boosting protocol whilst at the same time undergoing intensive therapy and or using meditations that promote positive self-esteem at the same time. The therapy/meditation will stimulate the development of new positive self-esteem pathways in the brain and the extra BDNF will increase the results. Another example I frequently see and have experienced myself is when people emerged from a prolonged period of depression discover they have experienced a loss of mental function, they may find they can’t study or concentrate as well as they used to, what they could do is redo the BDNF increasing protocol whilst engaging in daily brain training exercises that challenge the brain to perform the thing that it’s now finding difficult to do. I’m only just beginning to experiment with this possibility but what I’m hoping is that the combination of boosting BDNF at the same time as performing brain training therapy exercises and meditations to target qualities we want more of in a life may be a useful therapy enabling us to literally sculpt our brain to become better at doing the things we want more of in a life.

The pictures opposite[i] are great illustrations of the brains ability to change.
These are images of real neurons from rats either kept in a standard cage with little stimulation or from rats living in a more stimulating activity enriched environment. In the first picture you can clearly see an increased number of dendrite branches in the cell on the right from the brain of a rat living in an enriched environment compared to the cell on the left of a rat living in an under-stimulated environment.
 
The second picture shows close-ups of the dendrites, the images are in pairs on the left of each pair is from a rat housed in a standard environment and on the right we see the effects of just 3 weeks living in an enriched more s develop timulating environment. We can clearly see more tiny little buds called dendrite spines on the neurones on the rat living in an enriched stimulating environment, each of these dendrite spines forms a synapse connection with a dendrite branch from a neighbouring neuron, imagine millions of neurones sprouting hundreds of millions of new dendrite branches and spines, the result is a much more densely networked and connected brain.
 
By using the techniques below you could produce even better results than the rats in this experiment, the only thing that changed for them was the amount of external stimulating activity, but for optimum results you can combine focused brain training exercise with a diet, exercise and supplement protocol to increase BDNF levels at the same time.
 
Part of the physiology of bipolar syndrome (I have bipolar syndrome type II) is hyperactivity in the body’s stress responses (HPA axis) which simultaneously causes an increase in the production of inflammation in the brain and a decrease in the production of protective BDNF.
 
Chronic inflammation combined with decreased protection from BDNF can take a toll on the health of the brain and by my mid 40s I noticed signs of mild cognitive impairment (MCI) with a decline in my hearing, facial recognition and ability to do mental arithmetic; remembering faces and mental arithmetic had been always been things I was good at. 
 
My ongoing research into more effective ways to treat mental health problems both my own and my patients led me to BDNF; discovering that BDNF not only offered the potential to improve my mental health condition but it also had the potential to combat the MCI I was starting to notice was very exciting, I remember immediately thinking what is this BDNF and how I get a hold of it.
 
I was delighted to discover that there was quite a bit of research identifying natural remedies that have BDNF boosting properties and I decided to experiment on myself and see what would happen if I took all the known natural remedies boots BDNF at the same time combined with another course of relaxation brain training and an anti-inflammatory diet
 
Originally my focus was entirely developing a new technique to treat the underlying physiology of bipolar syndrome however I was delighted to experience the unexpected side-effects of full reversal in my mild cognitive impairment. Within a few months my facial recognition felt completely normal how it used to be, doing mental arithmetic felt like something I could do whereas it had become something I felt was beyond me, although still feel I need to do a bit more practice on the latter to fully regrow the neural pathways associated with this ability and the improvements in my hearing were dramatic. Not only did I notice my hearing returned to normal but seems to have improved to become better than it was in my 20s! I believe this to be so because while I was on my BDNF boosting prescription I started to understand for the first time the lyrics of many songs that I’ve been listening to since my 20s (in the 1980s) but previously never understood the words; unfortunately understanding the lyrics has ruined many of the songs I’ve been happily listening to since the 1980s. Nothing else has changed, I have not for example upgraded my hi-fi since 1997 and so I believe I’m hearing the lyrics for the first time because boosting BDNF has upgraded my brain.
 
Following my personal success I began using the technique in my practice in 2014 initially for my patients with intractable mental health problems and problems resulting from long-term prescription medication use, it quickly began to change lives and today I routinely recommend BDNF boosting prescriptions. 
 
If you’re interested in treatments for mental health problems including depression, bipolar syndrome and OCD I have an alternative book on boosting BDNF for these problems.
 
While studying the scientific research on BDNF as it related to mental illness I repeatedly came across research relating BDNF to cognitive impairment and Alzheimer’s disease.
 
It was seeing improvements in cognitive performance of my patients and experiencing first-hand reversal of MCI in myself together with the breakthrough reversal of cognitive impairment with Dr Bredesen’s treatment that gave rise to this book.
 
I’d like to make a disclaimer here so that you can make an informed decision:
My BDNF boosting brain regenerating technique has not been scientifically tested and therefore from a scientific point of view all the improvements I’m claiming are purely anecdotal; furthermore the breakthrough study by Dr Bredesen only involved 10 people and was not placebo-controlled. 
 
All the techniques and remedies used in both Dr Bredesen’s and my BDNF boosting treatments are natural and safe, however you are responsible for your own health and must consult with your doctor before considering discontinuing any prescription medication or combining it with any of the treatments discussed in this book.  The information in this book is for people that don’t want to wait for further scientific study into these methods, but instead want to go ahead with self-help personal experimentation. Unfortunately scientific investigation into the use of naturally remedies and holistic functional medicine techniques progresses at a snails pace because it never attracts the same financial backing that research into patentable and potentially profitable drugs attracts; it’s entirely possible that because of this simple economics the techniques described in this book may never become mainstream.
 

BDNF Isn’t Snake Oil

When you first hear about neuroplasticity you may wonder how far you can take it, well unfortunately there are limitations and you can’t completely grow a new brain! We need to be realistic with our expectations, you couldn’t for example grow new brain a child with autism or someone with schizophrenia by combining brain training and BDNF boosting remedies, BDNF isn’t snake oil or a miracle cure. There are genetic constraints imposed upon the way the brain is structured and person with autism will retain their autism through life; I’ve used my BDNF boosting protocol on myself twice but I still have bipolar syndrome, however doing this treatment did significantly improve my mental health. So far I’ve experienced a two thirds reduction in my cycling rate so that now would no longer be classified as even having rapid cycling, I was also able to give up several remedies I used to depend on and noticed significant improvement in various aspects of my brain function [REPEAT]; I’ve also had positive feedback from my patients, particularly patients with drawing and recovering from the side effects of prescription medication.
 

How to regrow lost synapses and repair depleted pathways Synapses

Firstly we’ll look how you would with the way we to boost BDNF.
Secondly we’ll look at additional remedies that promote regeneration and brain health.
Lastly will look at how to tailor make a protocol for your own individual condition.
 

Natural Remedies that Specifically Raise BDNF

 
Once you’ve got everything above in place you ready to take the remedies and grow new synapses :-)
 

Curcumin (Turmeric) & Piperine Combination

 Lots of research has shown the active ingredient in turmeric called curcumin raises BDNF levels [i] [ii] [iii] and produce an antidepressant effect.  Curcumin always held this tantalising promise of being a useful antidepressant but it never delivered because whole turmeric also contains compounds that drastically block the absorption, to get around this problem in most of the animal studies the curcumin was injected of curcumin but for many years I could never get enough of it into the human brain using supplements to reproduce the therapeutic antidepressant effects produced in animals studies; this problem is now a thing of the past.
 
An effective way to improve curcumin absorption is to preload your body with an extract from black pepper called piperine.
 
Piperine

Piperine is another remarkable natural compound extracted from black peppercorns.
 
There are 2 reasons to include piperine in your brain regeneration protocol:
Firstly piperine enhances the absorption of medicines including curcumin.
Secondly piperine has BDNF boosting, neuroprotective and antidepressant effects against stress induced depression all of its own[iv] [v].
 
In terms of absorption what piperine does is it inhibits the enzymes that break down curcumin thus protecting and delivering more of it to the brain. Piperine has been shown to increases the bioavailability of curcumin by a staggering 20 times or 2000% [vi] and most importantly taking piperine at the same time as curcumin has been proven to produce stronger therapeutic effects than either one alone, when combined with curcumin piperine produced a stronger anti-inflammatory and neuro protective effect against stress[vii], it enhanced the neuroprotective effect of curcumin  against stress induced cognitive decline [viii] and produced a stronger antidepressant effect specifically against stress induced depression[ix].
 
Another great thing about piperine is it’s cheap you can get a 2 month supply for as little as $6!
 
To get the most out of your curcumin/piperine combination you should give the piperine a head start (40 minutes should be enough) to get into the system so that by the time the curcumin starts to be absorbed from the intestines piperine is already in place to inhibit the enzymes that break down the curcumin. In practice achieving this is simple all you have to do is take the piperine just before or at the start of a meal, chew the tablet to break it down quickly and take your curcumin after your meal.
 
CAUTION:
Piperine can so significantly improve the bioavailability medicines so it should not be combined with pharmaceuticals because it may increase and altar the dosage you receive a.
 
Curcumin/Turmeric
 
In 2014 a technique was developed to wash out the absorption blocking compounds leaving the curcumin behind, this process is sometimes called BCM-95 and the manufacturers claim it improves the bioavailability sevenfold compared to unprocessed turmeric. I trialled this delivery system using Super Bio Curcumin from Life Extension and found it took 3-4 capsules a day to work but at this dose it becomes quite expensive.
 
I tried another product: CurcuBrain from Now Foods which is about the same price as the Super Bio Curcumin but seems slightly stronger requiring only 3 capsules a day.
 
A problem with these products is that the manufacturers go to great lengths to remove the compounds that block the absorption of curcumin but then if you eat a meal containing turmeric or several other spices at the same time as taking these products can end up at least partially undoing all of their good work by ingesting compounds that block curcumin absorption and as I eat curry several days a week so this would mean giving up my favourite dish.
 
If you follow a low salt diet to avoid hypertension you have to rely on herbs and spices to make your food tasty so rather than giving these up you can get around the absorption problem was simply taking enormous quantities of whole turmeric so that enough curcumin gets through to the brain. One option is to make up your own capsules from organic turmeric powder but you have to take 6 capsules twice a day which is a lot to swallow especially on top of all the other capsules will be taking.
 
A more practical option is simply taking a desert spoon of turmeric powder in a small glass of fruit juice twice a day after meals. Initially this idea sounds like it would be too unpalatable however you may be surprised to discover it isn’t that bad and in a couple of days you get used to the bitter taste. When combined with piperine I now highly recommend this way of delivering curcumin.
 
Which curcumin/turmeric to choose?
 
The CurcuBrain and Super Bio Curcumin may produce a superior effect, to whole turmeric powder, to be honest I only say that on the basis that the manufacturers claim their products linger in the blood stream longer than the combination of raw turmeric plus piperine. You may also find swallowing a few capsules is also more convenient than a tumbler full of turmeric after a meal. There are however two downsides to using these products firstly to receive their full benefits you would need to avoid eating turmeric at and other spices at the same time and secondly they’re more expensive. Convenience and maximum therapeutic benefit on your top priorities and cost is not an issue.
 
Alternatively if cost is an issue and you may even prefer not to swallow capsules then choose the whole powder option, at 2 desert spoons a day combined with piperine whole turmeric powder produces powerful results.
 

Very low-dose Lithium

You may be surprised to see me mention lithium on a site about natural therapy solutions because lithium is often thought of as a drug with the toxic side-effects but it’s mistaken to think of lithium as a drug isn’t it’s a nutritional mineral and when used at much lower doses than the doses used to produce a drug like affect it’s perhaps the most nutrient for promoting brain health. Lithium is needed to control an enzyme called GSK3, excessive amounts of GSK3 is involved in bipolar syndrome, sleep cycle disorders, diabetes Type II and buildup of amyloid plaque in the brain associated with Alzheimer’s disease.
 
The type of lithium I use in my practice is either a very low dose lithium orotate or an ultra-low-dose form of lithium derived from a product called Lithinase.
 
Lithium supplementation increases BDNF activity[x] and literally builds brain grey matter[xi] 8/10 persons given lithium showed an increase in brain grey matter of 3% after only 4 weeks. Lithium therapy shows promising results in regenerating the brain damage following stroke. Lithium may also protect cells from ageing and extend our life expectancy. In areas where there is more lithium in the drinking water there is a reduced rate of suicide and violent crimes [insert reference].
 
To treat bipolar syndrome a typical dose of lithium might be 180 mg of lithium from lithium carbonates in my practice I would use 5 mg which is a mere 1/36th or 2.7% which is nowhere near the toxic dose. You wouldn’t worry about supplementing a standard dose of zinc or magnesium just because taking 34 times the standard dose could be toxic and in the same way you shouldn’t worry about taking a few milligrams of lithium, I’m hoping to update your information and change your mind that lithium is not something you want to avoid because it has terrible side-effects but something you absolutely want to take every day to keep your brain healthy. In one study at doses as low as 0.3 mg lithium was shown to halt cognitive decline in patients with Alzheimer’s disease [xii] and this is important because it proves that lithium can exert a therapeutic effect on the brain at fractions of the doses normally used to treat bipolar mania. 
 
For unipolar depression studies have shown it can enhance the effectiveness of antidepressant drugs in cases of treatment resistant depression and I recommend using lithium for at least several months in the beginning of treatment, however given its neuroprotective effects you may want to continue to take it at low dose indefinitely.
 
For bipolar depression and cognitive decline I recommend lithium for long term use.
 
{{add lithium and suicide}}
 
I typically prescribed from 1 to 10 mg of lithium from lithium orotate for my patients with bipolar syndrome and to regulate the timing of the biological clock for sleep disorders and general brain health I often prescribe a minuscule 0.1 mg (100 mcg) of lithium from a product called Lithinase which is a mere 1/1700th or 0.06 % of the pharmaceutical dose.  Anybody interested in maintaining the long term health of their brain could but 5 mg tablets and take one quarter a day either with food or added to a drinking water bottle.
 
The image opposite is from a bipolar brain before and after lithium treatment. Notice the white line between the outer grey and inner white matter in the scan on the left, that white line shouldn’t be there it’s a sign of shrinkage; the image on the right is same brain after lithium treatment, the regeneration is clearly visible.
 
On a microscopic level before treatment would be on the left and after treatment on the right shows the growth of dendrites and synapses. 
 
For more information on lithium supplements see Lithium Friend or Foe UNDER CONSTRUCTION
 
Zinc
 
The essential nutritional mineral zinc is needed by literally hundreds of chemical reactions in the body and zinc deficiency can have wide reaching effects furthermore zinc deficiency may be very common especially amongst people with a poor diet ready-made meals and vegetarians.
 
I always called zinc the most mental mineral because of its propensity to have big effects on mood and anxiety disorders; my clinical observation you are a a a is that some people suffering from depression with social withdrawal can experience quite transformational benefits from a combination of high zinc and B6 supplementation (always take a B complex as a foundation when you’re going to elevate the dose of one individual B vitamin to prevent imbalance and when you supplement zinc you should also supplement a small amount of copper and iron to prevent the zinc depleting copper and iron levels). 
 
Increased dietary zinc intake in the diet is associated with a lower incidence of depression[xiii] and zinc supplementation increases BDNF and decreases depression[xiv] [xv] [xvi].
 
A great way to consume lots of zinc is by eating oysters or mussels, mussles are also an eco-friendly way to grow first-class protein.
 
Zinc is not that easily absorbed and you should always choose high-quality supplements. Until a few years ago I would recommend zinc gluconate or picolinate, which are still good but if you can find it used zinc supplements that made with the yeast Saccharomyces cerevisiae sometimes called Food State or True Food supplements they are better. Passing the zinc through a living organism attaches more of the it to protein and organic molecules which significantly improves absorption in the small intestines, these forms of supplements can also be taken on an empty stomach without causing nausea, this enables us to take zinc last thing at night which can aid sleep. Brands include Natures Own, Cytoplan and MegaFood.
 
Supplement 30 to 50 mg in the gluconate or picolinate form of 15 to 30 mg in the S. cerevisiae food state form. As mentioned to stop zinc depleting copper and iron you should also be using a multi mineral containing these, in order to work zinc also needs B vitamins as cofactors particularly B6 so take a B complex supplement but avoid folic acid as it causes inflammation and inhibits neurotransmitter production (see later), instead only use products using methylfolate. You could take multi vitamin/mineral such as Dr Best Best Multiple 2-3 capsules a day plus L-OptiZinc or Natures Own Food State zinc 1 or 2 a day.
 

Magnolia Extract 

Magnolia has traditionally been used in herbal medicine for the treatment of depression and anxiety disorders. Magnolol one of the medicinal compound found in magnolia restores healthy BDNF levels and repair serotonin pathways in the brain[i]. Magnolol may also repair function to the glial cells in the brain that support the neurons[ii] which makes it worth including in the basic brain regenerating formula as new research is showing that there can be significant reductions in the number of glia cells in the brains of people with major depression and bipolar syndrome[iii].

As a supplement magnolia is often combined with another herb called phellodendron in a proprietary Chinese herbal formula called Relora. I would recommend taking 2 capsules of Relora a day and 2 capsules Magnolia/calendula bark extract on its own. Divide the capsules between two meals.
 
N.B. when purchasing Magnolia it’s the extract from the bark that contained the beneficial magnanol.
 
Dogbane Leaf (Apocynum Venetum herb)
(Luo Bu Ma Ye)
 
[i] Phytother Res. 2012 Aug;26(8):1189-94. doi: 10.1002/ptr.3706. Epub 2012 Jan 5. Antidepressant-like effect of magnolol on BDNF up-regulation and serotonergic system activity in unpredictable chronic mild stress treated rats. Li LF1, Lu J, Li XM, Xu CL et al.
[ii] Eur J Pharmacol. 2013 Jul 5;711(1-3):42-9. doi: 10.1016/j.ejphar.2013.04.008. Epub 2013 Apr 28. Magnolol treatment reversed the glial pathology in an unpredictable chronic mild stress-induced rat model of depression. Li LF, Yang J.
[iii] CNS Neurol Disord Drug Targets. 2007 Jun;6(3):219-33. Gliogenesis and glial pathology in depression. Rajkowska G, Miguel-Hidalgo JJ.
 

Acetyl-L-Carnitine

The Dosage used in rat antidepressant experiments was 100 mg/Kg i.p.
The standard dose for L-carnitine is between 500-2,000mg.
There are various forms of carnitine supplementation available.
 
The equivalent dosage range for other forms of L-carnitine are as follows:
 
Acetyl-L-Carnitine (ALCAR) is used for cognitive enhancement.
Dosage: 500-2,500mg (ALCAR),
 
L-Carnitine L-Tartrate (LCLT) is typically used for physical performance and power output.
Dosage: 1,000-4,000mg (LCLT)
 
Glycine Propionyl L-Carnitine (GPLC) is used to alleviate intermittent claudication and blood flow issues.
Dosage: 1,000-4,000mg (GPLC).
 
Polygala Root (Yuan Zhi)
 
Gastrin, Gastrodia Root (Tian Ma)[xx]
[xxi]
Asia Pac J Clin Nutr. 2007;16 Suppl 1:305-8.
Effects of gastrodin on amino acids after cerebral ischemia-reperfusion injury in rat striatum.
Bie X1, Chen Y, Han J, Dai H, Wan H, Zhao T.
Author information
Abstract
The aim of this study was to explore the effect of gastrodin on the level of amino acids in the striatum in the rats of cerebral ischemia-reperfusion injury. 30 male SD rats were randomly divided into 3 groups: the group of pseudo-operation (normal control group, NC group), the group of cerebral ischemia-reperfusion injury (CIRI group), and the group of cerebral ischemia-reperfusion injury treated with gastrodin (G group). Cerebral ischemia-reperfusion injury was induced through middle cerebral artery occlusion (MCAO). 10 minutes before the operation, the rats in the G group were injected with gastrodin (50 mg/kg) intraperitoneally once. The rats in the CIRI and NC group were injected with the same volume of 10% propylene glycol normal saline intraperitoneally once. The levels of glutamic acid (Glu), aspartic acid (Asp), gamma-aminobutyric acid (GABA), taurine (Tau) in striatum in the rats of the 3 groups were measured with the method of microdialysis-HPLC techniques. The ratio of Glu to GABA was calculated. The volume of cerebral infarction was quantified. This study showed that gastrodin can decrease the volume of cerebral infarction, ameliorate the cerebral injury in the rats of cerebral ischemia-reperfusion. The mechanisms might be that gastrodin can improve the level of amino acids in striatum.
 
Gastrodia also possesses antidepressant effects it appears to increase the life span of dopamine and serotonin, one study showed it to be as effective as Prozac (fluoxetine) [xxii] [xxiii].
 
 

Alpha GPC (glycerophosphocholine)

 
 

Citicoline CDP Choline

 
 

Uridine

Uridine is a precursor or building block used to build synaptic membranes, when combined with increased BDNF it can increase the growth of synapses.
it also increases energy in the liver by supporting the health of mitochondria in the liver, used in combination with liver cleansing herbs it may potentiate the action.
 

DHA
 

Chinese Herbal Formulations

Several Chinese herbal formulas (Xiao Yao San[xxiv], Suyu-Jiaonang[xxv] and Danzhi Xiaoyao  [xxvi]) have been researched and shown to improve BDNF levels and have an antidepressant effects.
 
Another Chinese herb called Polygala tenuifolia has also been shown up regulate BDNF and repair neurons damaged by stress[xxvii].   
 
Ginkgo Biloba
 
Ginkgo biloba is a herb known for its effects on improving blood circulation in the brain. Ginkgo has been shown to increase BDNF levels and enhance the effectiveness of antidepressants in stress induced depression whilst at the same time mitigating the side-effects of the antidepressants[xxviii]; so if you are on antidepressants you may want to combine them with ginkgo for a better result (please consult with your physician first). Ginkgo was also shown to reduce oxidative stress, boost BDNF and cognitive function in ageing female rats [xxix].
 
Include ginkgo biloba in your BDNF boosting protocol if you wanting to work on cognitive decline especially if there isevidence of reduced blood circulation/oxygenation to the brain.
 

Eugenol Clove extract

SEE UPDATED TEXT IN ALZHIMERS BOOK
Cloves contain a compound called eugenol which has many powerful medicinal effects: it boosts BDNF, is antidepressant, it kills yeast and bacterial overgrowth in the intestines, it lowers blood sugar and may treat Alzheimer’s. Pure clove oil contains 80-95% eugenol and whole cloves contain about 14-20% essential oil.
 
Eugenol has multiple antidepressant properties it enhancing serotonin, dopamine and norepinephrine activity comparable to the antidepressant drug imipramine[xxx][xxxi], it also boosts antidepressant BDNF levels. You may already be familiar with another property of eugenol, it’s the thing in clove oil that can be rubbed on the gums as an dental analgesic.
 
I must admit I haven’t tried the effectiveness of eugenol on its own as an antidepressant, if you do please share your experiences with me.
 
There’s a growing body of scientific evidence that suggests eugenol can be used as a drug treatment for Alzheimer’s disease[xxxii]. So if you’re interested in regenerating your brain because of Alzheimer’s or cognitive decline include clove oil/eugenol in your prescription.
 
Eugenol is a powerful antifungal and antibacterial which can be used to treat intestinal candida or yeast overgrowth and SIBO (small intestines bacterial overgrowth). Intestinal disbiosis from yeast or bacterial overgrowth can inflame the intestinal wall and weaken its integrity, this is often called leaky gut syndrome. A healthy intestinal wall prevents large half-digested food molecules passing through the intestinal wall into the blood, with a leaky gut syndrome however un-healthy amounts of big half-digested food molecules leak through into the blood which provokes the immune system and increases the release of inflammatory cytokines throughout the body. If the half digestive food molecules make it not only through the intestinal wall but also pass through the blood-brain barrier they provoke the immune system in the brain itself. This is referred to as a leaky gut-brain-axis and may cause sufficient chronic inflammation in the brain to prevent you increasing your neuroplasticity and achieving regeneration; a leaky gut brain axis should therefore be taken seriously and treated aggressively. Eugenol can be a helpful remedy when yeast and bacterial overgrowth are contributing to a leaky gut-brain-axis. See my pages on candida treatment leaky gut syndrome and the gut-brain-axis UNDER CONSTRUCTION.
 
Clove is also a digestive stimulant in general so include it in your prescription if you suffer from indigestion.
 
Eugenol lowers blood sugar and at therapeutic doses this effect can be quite powerful, this may be something you want or something you want to avoid. Remember high blood sugar can prevent your brain from being able to regenerate because it causes inflammation, reduces BDNF and neuroplasticity, so if you’re struggling to bring down high blood sugar you definitely want to consider including eugenol in your prescription. On the other hand if you’re prone to bouts of low blood sugar (hypoglycaemia) temporarily depriving your brain of energy you may not want to include eugenol, you can safely experiment with eugenol and see if in your case it’s produces bouts of hypoglycaemia. 
 

Clove Oil Dosage

The therapeutic dose is 1-2 drops (of clove oil) for every 10 kg you weigh.
i.e. if you weigh 80 kg you take 8-16 drops in total in a day but that should be divided between 2 doses i.e. 4-8 drops with breakfast and 4-8 drops with dinner.
If you weigh 60 kg you take 6-12 drops in total in a day divided between 2 meals i.e. 3-6 drops with breakfast and 3-6 drops with dinner.
If you work in pounds that’s 1-2 drops for every 22 pounds of your body weight so if you weigh 176 pounds, divide that by 22 gives you 8 so you going to take 8-16 drops in total or 4-8 drops in the morning and 4-8 drops in the evening.
 
A 60mls (2 oz) bottle is more than enough for a 3-4 month cause and you can use up any surplus leftover in cooking or mulled-wine at Christmas. 
 
 

This Clove or Safe Internally?
 

Online you will see many sites saying do not take essential oils internally and I agree with this general advice. When proposing to take an essential oil internally you need to be absolutely certain it’s safe because there are essential oils that are toxic when taken internally, clove oil however is not one of them.
 
There was a case of severe toxicity when a 2 year old child ingested 5-10 mls in one go, I’ve not tied it but I’m pretty sure if I ingested a 10 mls dessertspoon of clove oil in one go it would give me burning stomach ache, indigestion, nausea and maybe make me vomit, so clove oil has a kind of inbuilt safety, the discomfort will limit the dose you can take to below toxic amounts anyway. Animal experiments found the LD50 (lethal dose 50%) of pure eugenol is above 2650 mg per Kg that’s like an adult man taking 212,000 mg (212 grams) in one go.  Very roughly I estimate that would involve taking over 250 mls approximately ½ a pint of clove essential oil in one go! In contrast I’m proposing you use 60 mls over about 3 to 4 months.
 
In summary clove oil is a powerful medicine and the few drops of clove oil needed to produce a therapeutic effect are not anywhere near toxic doses.
 
There are 2 more considerations:
One is that essential oils are concentrated from a lot of product so to avoid concentrating pesticide residues always buy high quality organic essential oils.
The 2nd consideration is undiluted clove oil is very burning so do not take it neat you must dilute the dose in sufficient water/juice/milk; you can combine it together with the turmeric for a really strong medicinal flavour!.
 
CAUTION:
Clove and eugenol can have negative interactions with blood thinners always look up drug interactions.
Safety during pregnancy or breastfeeding is unknown so don’t take it.
Like many things clove can cause allergies. Test to make sure you’re not allergic by putting a crop of clove oil in a desert spoon of olive oil then apply a small amount of this mixture to your inside arm with a cotton bud if there is no reddening of the skin in 24 hours it’s highly unlikely you have an allergy.
 

Alpha Linolenic Acid

Alpha linolenic acid is an omega-3 oil found in vegetable oils particularly flaxseed, hemp and perilla. It can be converted into the omega-3 oils EPA and DHA found in fish oil that are important for mental health. The rate of conversion of alpha linolenic acid to EPA and particularly DHA is very low however which can present a problem for vegetarians and vegans.  Alpha linolenic acid has been shown to increase BDNF activity and assist regeneration of the brain following strokes [xxxiii] [xxxiv].
 

To Boost BDNF Levels:

 
To Boost BDNF Levels:
 
1/ Reduce our exposure to anything that damages brain cells and uses up precious BDNF, we want as much BDNF available for regrowth as possible and not wasted on just protecting our brain from toxic stress and inflammation.
Avoid :-
 
  • Smoking, (pure nicotine however actually boosts BDNF so if you smoke can switch over to nicotine patches or gum and continue using them throughout the treatment).
  • Fried foods because they flood the body with free radicals, use low-temperature sautéing in a watery environment instead.
  • Wheat and maybe all gluten containing grains (at least go wheat free),
  • During the BDNF boosting protocol give up alcohol.
  • Eating a diet rich in omega 6-oils and deficient in omega-3 oils which basically means avoiding all ready-made meals, processed foods and eating lots of fish or fish oil supplements.
  • Trans-fats which are found in ready-made meals, margarines, ready-made biscuits cakes et cetera.
  • High GI foods.
2/ Eliminate things that reduces BDNF production such as elevated levels of the stress hormone cortisol.
3/ Increase BDNF production with remedies and exercises.
 
 
Controlling stress responses is essential
Let’s recap the brains of people with chronic depression, bipolar and anxiety overproduce stress responses via hyperactive via the HPA-axis and in this section you can learn how to stop that happening.  
 

Changing Stress Physiology Is Key to Success

Chronic stress responses from a hyperactive HPA-axis attack our brain in 2 ways, firstly they produce chronic inflammation and secondly they decrease the production of BDNF the very thing we need more of to protect ourselves from the chronic inflammation.
 
One of the actions of the stress hormone cortisol is to aggressively activate our immune system including the immune cells in our brain, these cells release inflammation promoting chemicals called cytokines. A short-term elevation in cytokines and inflammation to fight an infection for example is not a problem but when cytokines remain persistently elevated it wears down the health of the neurones so that eventually neural networks can break down.
 
In some situations source of the stress responses causing mental health problems may be obvious, a bereavement for example, however in people with endogenous mental health problems the problem seems to be for no apparent reason and unrelated to external sources of stress. In some people their neural pathways may be already pushed to the verge of breaking down from a hyperactive HPA-axis and it only takes a little push from external sources of stress to produce a break down.
 
Furthermore it now seems that there are genetic differences in the way peoples brains respond to stress, in some people chronic stress responses reduce BDNF levels resulting mental health problems whereas other people may possess brains that are more resilient to elevated stress levels. I’m not going give any references for this because the science is changing so rapidly.
 
Hypothetically it’s possible that having a brain that over produces stress responses and having a brain that’s easily damaged by stress hormones are two independent things i.e. you could have a brain that over produces stress responses but is quite resilient to the effects, alternatively you could have a brain that doesn’t excessively produce stress responses but nevertheless is highly vulnerable to damage from stress, or you could have a highly stressed and highly vulnerable brain. 
 
Another phenomenon is that we can become completely habituated to chronic stress responses so that we no longer feel we’re stressed, I often meet such people in my practice, they have long since lost any sensations or awareness that they are heavily over-producing stress responses which can make it hard for them to believe this issue relates to their condition, but exaggerated stress responses are an integral part of the physiology that causes these problems and changing this physiology is an essential part of your recovery. You have to do the relaxation response brain training exercise for the brain regenerating protocol to work, not doing so is likely to lead to failure, it’s a dealbreaker.
 
 
There are two pathways through which stress in the mind communicates with the body to produce a stress response I think of one as a wired route and the other like Wi-Fi; the wired route travels along the nerves of the autonomic nervous system from the brain down the spinal column and then into the body, the stress response produced by the autonomic nervous system clamps our intestines for example and may contribute to irritable bowel syndrome, the Wi-Fi route distributes stress hormones throughout the body this is the HPA-axis.
 
In PTSD for example you can imagine the HPA-axis being constantly switched on by repeatedly reactivating or reliving the original psychological trauma; in people with depression and bipolar syndrome it may not be so obvious that there is excessive firing of stress responses however there are studies showing that the HPA axis becomes chronically overactive and enlarged in people with these conditions. . If you have chronic depression or bipolar syndrome this is another important thing to know and change.
 
The autonomic nervous system has 2 sides, in a sense it’s always on it either producing a stress response (synthetic dominant) or a relaxation response (parasympathetic dominant); the HPA-axis on the other hand is either on or off
 
as far as I know no one is sure we have increased stress responses because of the mental illness or do we have mental illness because we overproduce stress responses, I’m not too bothered about knowing where it starts or which is the chicken and which is the egg here, my solution is to radically change the way the body processes stress responses with intensive training.
Stress in the mind of the hypothalamus (H) to tell the pituitary (P) to tell the adrenals (A) to release the stress hormones adrenaline and cortisol, this is the HPA axis, a major pathway whereby stress in the mind is communicated to the body. It has been observed that the HPA axis of people with depression bipolar and anxiety are often enlarged compared to the general population meaning to say that we fire above average levels of stress signals into our body. You may or you may not be aware these stress responses, in fact many people habituated or get used to the stress responses so that they no longer consider themselves to be stressed.
To maximise your chances of recovery from any mood or anxiety disorder pay no regard to whether or not you do or don’t consider yourself to be a stressed person, instead simply presume for the purposes of treatment that you are overproducing stress responses and have an enlarged HPA axis, neural networks and the psychology to activate it, and then undergo the relaxation response training programme to shrink and diminish all the above.
As already mentioned stress and specifically the stress hormone cortisol decreases BDNF levels and promote inflammation in the brain which damages brain cells and neuronal networks. You can significantly change the way that your brain produces stress responses with a two pronged approach: firstly over a three-month period you can learn how to switch on the relaxation response in your body and switch off the stress response, you can do this by performing a modified yoga exercise every day for half an hour for 100 days. Research has shown that we can actually change the shape of the brain and develop new pathways in as little as eight weeks of daily practice of meditation technique called mindfulness-based stress reduction, in my practice I prescribe a minimum of 100 days or 14 weeks Relaxation Response Training to change the way your system deals with stress responses and hardwire this change into your brain.
What’s interesting here is that were trying to not only diminish stress levels in the brain that diminish BDNF levels but were also trying to grow new pathways in the brain and growing new pathways requires adequate BDNF levels, so during the three months you’re doing the relaxation response training combine it with all the supplements and exercise techniques that increase BDNF levels to maximise the growth of growth and development of new pathways in the brain that switch on the relaxation response.
By increasing BDNF levels the supplements and exercise you will literally assist your brain to more effectively hardwire the relaxation response pathways your stimulating by repeated training into your brain and the more you do this the more you diminish chronic stress responses with further increases BDNF levels; you can create a positive upward healing spiral which can be literally transformational. I want to misinform you here I’ve never seen anybody completely cure depression, anxiety or bipolar syndrome in this way, but what I have repeatedly seen this this intensive therapy program start the healing process that continues over the next year or so.
The second approach to reducing unhealthy chronic stress responses in the brain is to remodel traumatic and stressful memories using psychotherapy techniques. In my practice I use cognitive hypnotherapy and NLP techniques as they are very direct and time efficient, CBT can also achieve quick changes; alternatively you may want to invest in a longer more in-depth form of psychotherapy. The effectiveness of talking therapies is very dependent on there being a good match or connection between the client and therapist and unfortunately I’ve met many people who tried psychotherapy and because it didn’t help they no longer believe in talking therapies. It’s almost impossible to remodel painful and traumatic memories by yourself and they will keep firing unnecessary stress responses that can diminish BDNF levels and may prevent you from fully recovering, so if at first you don’t succeed with one therapist try again…
 

Reducing Inflammation is Key to Success

Besides hyperactivity in the HPA axis there are several other sources of chronic inflammation that can affect the health of the brain these include:
 
exposure to free radicals (from smoking, poor diet particularly rich in fried foods and exposure to environmental toxins),
food allergies and sensitivities (gluten should be particularly singled out in this regard),
high blood sugar,
unhealthy intestines with a leaky intestinal wall that permits half-digested food to enter the bloodstream and provokes an immune response,
if a leaky gut wall is also coupled with a leaky blood brain barrier so that half-digested food molecules can pass from the blood into the brain across the blood-brain barrier this can provoke persistent inflammation.
 
Any one of these sources of inflammation could potentially prevent the brain regenerating protocol from working and so you must eliminate them all.  I’ll explain how to do that in the treatment section.
 

Diet and Lifestyle to Raise BDNF Levels

Above I said what to exclude now what to include
 
To create a sufficiently healthy cellular environment the best diet to follow during this program is the Mediterranean diet. You should also eat lots of antioxidants from green vegetables like broccoli, dark and read coloured berries like blueberries and pomegranates.
 
Improving blood sugar levels is essential
Eating a high sugar/high-fat diet reduces BDNF levels[xxxv], please note however it’s the combination of high sugar and fat that is the problem, the theory that the high-fat diet is unhealthy is now known to be wrong, you can eat egg yolks, lots of avocados, peanut butter, coconut fat, olive oil and omega-3 oils as long as you exclude high glycaemic index and sugary foods.
Another thing that reduces BDNF levels is having high blood sugar whether from type II diabetes, insulin resistance or prediabetes, also having high blood sugar can increase the risk of developing mental health problems. Conversely as we saw above stress can lower BDNF levels cause depression which in turn can increases your risk of developing blood sugar problems so it’s a two way street.
If you have high blood sugar or reactive hypoglycaemia you should work on these problems first before investing in the BDNF boosting protocol, not doing so do any harm it just might not be effective (see Low Blood Sugar & Mental Health Problems).
 
The best exercise to boost BDNF
Exercise is actually one of the best ways to increase BDNF levels in the brain, typically when we think of exercise we immediately park it in our mind as being just a generally good all-round thing, but I’m going to ask you right now to re-frame how you think of exercise and in the context of regenerating the brain you should see exercise as a way of literally obtaining an injection of BDNF.  Increased levels of BDNF from exercise have been shown to increase regeneration of damaged nerves cells[xxxvi].
If I told you about a pill you could swallow that would inject substantial quantities of BDNF straight into the parts of your brain that need it you’d probably want to take it, well that’s what exercise is and vigourous exercise injects the most. Exercise is not just some general helpful thing you should do, it’s a way of getting your hands on and delivering a shot of a chemical that repairs damaged parts of our brain.
A surprising finding was that strength training on its own does not increase BDNF levels[xxxvii], so being generally sedentary and doing strength training does not help us in our quest to regenerate the brain and recover from mental illness; having said that I still highly recommend strength training for the numerous alternative benefits including protecting us from weight gain and increased risk of type II diabetes. Engaging in vigourous aerobic exercise on the other hand does elevate BDNF levels[xxxviii] and the most efficient way to perform a robot exercise is called high intensity interval training (HIIT). HIIT takes very little time and requires no specialist equipment, it consists of doing any vigourous and exhausting movement for example squatting down and then doing a star jump or spinning on an exercise bike for 30 seconds at 100% of your capacity then resting for a minute and repeating twice more. By performing HIIT as little as three times a week or every second day can improve your BDNF levels and brain health.
Obviously if you haven’t exercised for a long time you shouldn’t go straight into exercising at 100% of your capacity and will need to start gently and build up, it might take you as much as three months to be able to perform this technique properly; if you’re very out of shape and or have a complicating medical condition it could take you even longer and you should consult with your physician and seek the guidance of a fitness trainer before embarking on such a regime.

Putting It All TogetherTo treat a mental health problem we want to improve the health of our brain, chronic stress responses, high blood sugar and inflammation downgrade the health of the brain by increasing the rate of cell death and decreasing the amount of protected BDNF. If you have high blood sugar start improving your diet and exercise regime to bringing down your sugar levels 1st and once you’ve achieved some progress with that you should undergo a relaxation response training programme and follow an anti-inflammatory diet; these steps will reduce elements that harm brain cells and allow BDNF levels to naturally rise. Once you start on the relaxation response training you can take natural remedies to boost BDNF levels at the same time and really kickstart regeneration in your brain and recovery from your condition.
 
The foundation BDNF boosting prescription:
 
L-OptiZinc
1 capsule twice a day with meals (along with B complex, copper and iron)
 
Curcumin either:
Super Bio Curcumin 2 capsules twice a day after meals or CurcuBrain one capsule after breakfast and 2 after dinner or one desert spoon of organic turmeric powder and a little fruit juice twice a day after meals.
 
Piperine
10 mg twice a day, chew the tablet just before meals, e.g. Source Naturals BioPerine)
 
Marigold and Relora
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Lithium either:
Either Lithinase 3 capsules twice a day with meals or for a much stronger effect
Lithium Orotate 2.5 mg (half a tablet) to 5 mg twice a day with meals.
 
HIIT exercise.
One session every day if possible, but at least several times a week.
 
Relaxation response brain training.
One 20 minute session a day taking your body into a profoundly relaxed condition and 5 mini relaxations lasting one and a half to 2 ½ minutes a day. Don’t skip out on this part of the prescription remember hyperactive HPA axis is probably what caused low BDNF/high inflammation brain degeneration in the first place.
 
Supportive Remedies:
I would always add Magnesium (say 600-800 mg from say magnesium citrate) because it is involved in so may cellular repair processes.
 
N.B. Avoid folic acid it can put a spanner in the
works:
We need the natural form of folate called methyl folate to control inflammation in our brain and make neurotransmitters. Some people have a gene mutation (see MTHFR gene mutation) that means that when they take the synthetic form of folate called folic acid it blocks their ability to make methyl folate leading to increased inflammation in the brain and decreased production of neurotransmitters. Folic acid is a cheap synthetic form of folate used in most multivitamins and B complex, if you have the stronger versions of the gene mutation and you take folic acid you’ll probably not make any progress.
 
The simplest way to avoid this potential problem is only use multivitamins and B complex containing L-methyl folate and not folic acid; alternatively you can have a test for the MTHFR gene mutation see my page MTHFR gene mutation.
 
Sleep and Melatonin
 
Make sure you get enough sleep so that you have no yawning or signs of sleep debt the following day.
Basically:
Let your body starts to cool down 3 or 4 hours before you want to go to sleep.
Block blue light entering your eyes the 2 ½ to 3 hours before you want to go to sleep.
Learn to control and switch off stress responses to prevent night-time cortisol keeping you awake.
The latest research If you want to learn how to master the physiology that controls sleep so that you can switch on deep refreshing sleep  see my book Sleep Better with Natural Therapies available from bookstores.
 
Use oral or transdermal melatonin if you want to. Melatonin
 
Follow a low red meat high vegetable diet ideally the Mediterranean style diet.
 
How to tailor the basic protocol to your individual needs:
 
For Depression
 
For severe depression include Apocynum venetum (Luo Bu Ma Ye), Polygala (yuan zhi) and clove extract. You could add acetyl-L-carnitine to increase cellular energy for a stronger effect or if exhaustion is a feature. ShiftK the out to start just say
 
For depression with anxiety try adding Polygala (yuan zhi) and/or Relora.
 
The depression with physical and mental exhaustion add acetyl-L-carnitine as carnitine is boosts cellular energy. This would also be a good choice for cognitive decline.
 
If you have twitching muscles, headaches or migraines include the Gastrodia.
 

For Bipolar Disorder

For bipolar depression and/or addictive thoughts add NAC cysteine 1000-1200 mg once or twice a day on an empty stomach. Take the NAC cysteine until the depression and/or addictive thoughts have abated then continue for a couple more months. I took NAC cysteine every day for 2 years myself and used to recommended it for long-term use as a good all-round detoxifier however there is a hypothetical possibility that long-term administration may make it harder for your body to kill cancer cells (not give you cancer just make it harder to kill cancer cells if you have them), this has to be weighed up against the sometimes very real possibility that bipolar syndrome may lead to drug or other addictions or death. Curcumin has powerful cancer-preventing properties unfortunately however NAC cysteine could hypothetically negate these properties, my personal plan is to take NAC cysteine for several months at a time whenever thoughts of interest in addictive things re-enter my mind and take piperine/curcumin on a continuous basis for long-term maintenance of brain health and its cancer-preventing benefits.
 
For decline in cognitive abilities which are common after repeated cycles of manic-depression add ashwaganda[xxxix] for at least 6 months to 2 years or even consider taking it on an ongoing basis (always miss out one day a week when you take the herb continuously)

For Cognitive DeclinePharmacognosy Res. 2014 Jan;6(1):12-8. doi: 10.4103/0974-8490.122912.
Effect of standardized aqueous extract of Withania somnifera on tests of cognitive and psychomotor performance in healthy human participants.
Pingali U1, Pilli R1, Fatima N1.
 
For Alzheimer’s Amyloid Plaque
 
Aswaganda[xl]
 
The High Blood Sugar, Insulin Resistance, Type II Diabetes
 
Include clove extract for your initial treatment phase and then stay on the piperine plus curcumin for a year. Long-term supplementation with curcumin has been shown to prevent the progression of an you are a you be well
 
If you have brain fog, memory loss and general signs of poor circulation with pale/purple cold fingertips and toes include the ginkgo biloba.

Duration of the Treatment and Maintaining the Improvements
 

Limitations and potential of the BDNF Hypothesis

 
Every time we latch onto the new big thing and hope that this is going to lead to a wonder cure for mental illness we are quickly reminded that brain science always complicated and contradictory, and this has also turned out to be the case with BDNF. In my practice I have long since given up the quest for a simple single cure-all, the causes of mental illness are multifactorial and it’s is too simplistic to say that low levels of BDNF is the sole cause of mental illness[xli] and hoping that increasing BDNF levels alone will be a simple cure; however this new approach is a major breakthrough and opens up completely new direction for treatment.
 
First big breakthrough in mental illness was that neurotransmitter deficiencies could cause mental health problems (the so-called catecholamine hypothesis), if memory serves this would have its origin in the 1950s, I believe the discovery that BDNF deficiencies can cause mental illness is the 2nd big breakthrough and is at least as useful as the neurotransmitter deficiency model.
 
Furthermore the BDNF deficiency model doesn’t contradict or overturn the neurotransmitter deficiency model it adds something and improves it. You can apply both these techniques together at the same time or if you’re not in a rush spent some time boosting BDNF and regenerating your brain first and then work on your neurotransmitter levels after that if you still need to.
 
I think another major thing to come out of the low BDNF model is how it explains and clarifies the central role of stress responses play in mental illness. It shows us how the hyperactive HPA-axis stress response found in people with depression and bipolar syndrome damages key structures in the brain and leads to mental health problems and therefore it shows us the critical importance of altering our stress physiology if we are to recover from mental illness and prevent relapse. It shows us that psychotherapy, relaxation response brain training and meditation techniques to release trauma and change our stress physiology actually produce chemical and structural changes in the brain.
 
I’m sure in due course the pharmaceutical industry will research and develop new drugs to stimulate regeneration of the brain rather than simply trying to boost deficient neurotransmitters, I developed my BDNF boosting protocol from the existing research in this area. Developing this new generation of drugs will probably take a very long time and they may come with side effects, in the meantime you can start straightaway boosting your BDNF levels with natural remedies.
 
 
[i] Xu Y, Ku B, Tie L, Yao H, Jiang W, Ma X, Li X (November 2006). "Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB". Brain Res. 1122 (1): 56–64. doi:10.1016/j.brainres. 2006.09.009.  PMID 17022948.
[ii] Neuroscience Letters Volume 493, Issue 3, 15 April 2011, Pages 145–148. Curcumin reverses corticosterone-induced depressive-like behavior and decrease in brain BDNF levels in rats Zhen Huanga, Xiao-Ming Zhonga, Zhao-Yi Lia, et.al.
[iii] Behavioural Brain Research. Volume 235, Issue 1, 1 November 2012, Pages 67–72. Curcumin produces antidepressant effects via activating MAPK/ERK-dependent brain-derived neurotrophic factor expression in the amygdala of mice. Lin Zhanga, et.al.
[iv] Life Sci. 2007 Mar 20;80(15):1373-81. Epub 2007 Jan 12. Antidepressant like effects of piperine in chronic mild stress treated mice and its possible mechanisms. Li S1, Wang C, Wang M, Li W, Matsumoto K, Tang Y.
[v] Neurochem Int. 2014 Jul;74:36-41. doi: 10.1016/j.neuint.2014.04.017. Epub 2014 May 9. Piperine reverses the effects of corticosterone on behavior and hippocampal BDNF expression in mice. Mao QQ1, Huang Z2, Zhong XM2, Xian YF3, Ip SP4.
[vi] Planta Med. 1998 May;64(4):353-6. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Shoba G1, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS.
[vii] PLoS One. 2013 Apr 17;8(4):e61052. doi: 10.1371/journal.pone.0061052. Print 2013. Suppression of neuroinflammatory and apoptotic signaling cascade by curcumin alone and in combination with piperine in rat model of olfactory bulbectomy induced depression. Rinwa P1, Kumar A, Garg S.
[viii] Brain Res. 2012 Dec 7;1488:38-50. doi: 10.1016/j.brainres.2012.10.002. Epub 2012 Oct 23. Piperine potentiates the protective effects of curcumin against chronic unpredictable stress-induced cognitive impairment and oxidative damage in mice. Rinwa P1, Kumar A.
[ix] Pharmacol Biochem Behav. 2009 Mar;92(1):39-43. doi: 10.1016/j.pbb.2008.10.007. Epub 2008 Oct 25. Anti-depressant like effect of curcumin and its combination with piperine in unpredictable chronic stress-induced behavioral, biochemical and neurochemical changes. Bhutani MK1, Bishnoi M, Kulkarni SK.
[x] Mol Psychiatry. 2009 Jan;14(1):51-9. Epub 2007 Oct 9. The mood stabilizers lithium and valproate selectively activate the promoter IV of brain-derived neurotrophic factor in neurons. Yasuda, Liang, et al.
[xi] Moore G.L. et al Lithium-induced increase in human grey matter. Lancet 2000; 356:1, 241-1, 242
[xii] Curr Alzheimer Res. 2013 Jan;10(1):104-7. Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer's disease. Nunes MA1, Viel TA, Buck HS.
[xiii] J Affect Disord. 2014 Sep;166:249-57. doi: 10.1016/j.jad.2014.05.016. Epub 2014 May 23. Dietary zinc is associated with a lower incidence of depression: findings from two Australian cohorts. Vashum KP1, McEvoy M2, Milton AH3, McElduff P4, Hure A5, Byles J6, Attia J7.
[xiv] Antidepressant activity of zinc and magnesium in view of the current hypotheses of antidepressant action. Szewczyk B1, Poleszak E, Sowa-Kućma M, Siwek M, Dudek D, Ryszewska-Pokraśniewicz B, Radziwoń-Zaleska M, Opoka W, Czekaj J, Pilc A, Nowak G.
[xv] Nutr Neurosci. 2014 Jan 7. Zinc monotherapy increases serum brain-derived neurotrophic factor (BDNF) levels and decreases depressive symptoms in overweight or obese subjects: A double-blind, randomized, placebo-controlled trial.  Solati Z, Jazayeri S, Tehrani-Doost M, Mahmoodianfard S, Gohari MR.
[xvi] Pharmacol Rep. 2005 Nov-Dec;57(6):713-8. Zinc and depression. An update. Nowak , Szewczyk , Pilc A.
[xvii] Phytother Res. 2012 Aug;26(8):1189-94. doi: 10.1002/ptr.3706. Epub 2012 Jan 5. Antidepressant-like effect of magnolol on BDNF up-regulation and serotonergic system activity in unpredictable chronic mild stress treated rats. Li LF1, Lu J, Li XM, Xu CL et al.
[xviii] Eur J Pharmacol. 2013 Jul 5;711(1-3):42-9. doi: 10.1016/j.ejphar.2013.04.008. Epub 2013 Apr 28. Magnolol treatment reversed the glial pathology in an unpredictable chronic mild stress-induced rat model of depression. Li LF, Yang J.
[xix] CNS Neurol Disord Drug Targets. 2007 Jun;6(3):219-33. Gliogenesis and glial pathology in depression. Rajkowska G, Miguel-Hidalgo JJ.
[xx] Neural Regen Res. 2013 May 25;8(15):1383-9. doi: 10.3969/j.issn.1673-5374.2013.15.005. Gastrodin promotes the secretion of brain-derived neurotrophic factor in the injured spinal cord. Song C1, Fang S1, Lv G1, Mei X1.
[xxi] Neurochem Res. 2014 Jan;39(1):172-9. doi: 10.1007/s11064-013-1203-0. Epub 2013 Nov 30.
Gastrodin ameliorates depressive-like behaviors and up-regulates the expression of BDNF in the hippocampus and hippocampal-derived astrocyte of rats. Zhang R1, Peng Z, Wang H, Xue F, Chen Y, Wang Y, Wang H, Tan Q.
[xxii] Am J Chin Med. 2009;37(6):1113-24. Rhizomes of Gastrodia elata B(L) possess antidepressant-like effect via monoamine modulation in subchronic animal model. Chen PJ1, Hsieh CL, Su KP, Hou YC, Chiang HM, Sheen LY.
[xxiii] Am J Chin Med. 2008;36(1):95-106. The antidepressant effect of Gastrodia elata Bl. on the forced-swimming test in rats. Chen PJ1, Hsieh CL, Su KP, Hou YC, Chiang HM, Lin IH, Sheen LY.
[xxiv] J Ethnopharmacol. 2010 Mar 24;128(2):336-41. doi: 10.1016/j.jep.2010.01.050. Epub 2010 Feb 4. Effects of SYJN, a Chinese herbal formula, on chronic unpredictable stress-induced changes in behavior and brain BDNF in rats. Mao QQ, Huang Z,
[xxv] J Ethnopharmacol. 2010 Mar 24;128(2):336-41. doi: 10.1016/j.jep.2010.01.050. Epub 2010 Feb 4. Effects of SYJN, a Chinese herbal formula, on chronic unpredictable stress-induced changes in behavior and brain BDNF in rats. Mao QQ1, Huang Z, Zhong XM, Feng CR, Pan AJ, Li ZY, Ip SP, Che CT.
[xxvi] Zhongguo Zhong Xi Yi Jie He Za Zhi. 2007 Mar;27(3):197-200. [Effect of Danzhi Xiaoyao Powder on neuro-immuno-endocrine system in patients with depression]. [Article in Chinese] Li YJ, Luo HC, Qian RQ.
[xxvii] Nan Fang Yi Ke Da Xue Xue Bao. 2009 Jun;29(6):1199-203. [Effect of Polygala tenuifolia Willd YZ-50 on the mRNA expression of brain-derived neurotrophic factor and its receptor TrkB in rats with chronic stress depression]. [Article in Chinese] Sun Y, Xie TT, Wang DX, Liu P.
[xxviii] Chin Med J (Engl). 2005 Mar 5;118(5):391-7. Effects of extract of Ginkgo biloba with venlafaxine on brain injury in a rat model of depression. Qin XS1, Jin KH, et al.
[xxix] Behav Brain Res. 2015 Feb 1;278:453-61. doi: 10.1016/j.bbr.2014.10.032. Epub 2014 Oct 30. The effects of Ginkgo biloba extract on cognitive functions in aged female rats: The role of oxidative stress and brain-derived neurotrophic factor. Belviranlı M1, Okudan N2.
[xxx] Brain Res. 2004 Jun 18;1011(2):243-6. Eugenol exhibits antidepressant-like activity in mice and induces expression of metallothionein-III in the hippocampus. Irie Y1, Itokazu N, et al.
[xxxi] Fundam Clin Pharmacol. 2013 Oct;27(5):471-82. doi: 10.1111/j.1472-8206.2012.01058.x. Epub 2012 Jul 25. Antidepressant-like effect of bis-eugenol in the mice forced swimming test: evidence for the involvement of the monoaminergic system.
do Amaral, Silva, et al.
[xxxii] Effects of Eugenol on the Central Nervous System: Its Possible Application to Treatment of Alzheimer's Disease, Depression, and Parkinson's Disease. Irie, Yoshifumi
Source: Current Bioactive Compounds, Volume 2, Number 1, March 2006, pp. 57-66(10)
[xxxiii] Nutr J. 2015 Feb 26;14(1):20. doi: 10.1186/s12937-015-0012-5.
Oral consumption of α-linolenic acid increases serum BDNF levels in healthy adult humans.
Hadjighassem M1,2, Kamalidehghan B3, Shekarriz N4, Baseerat A5, Molavi N6, Mehrpour M7, Joghataei MT8,9, Tondar M10, Ahmadipour F11, Meng GY12.
[xxxiv] J Ethnopharmacol. 2013 May 2;147(1):245-53. doi: 10.1016/j.jep.2013.03.015. Epub 2013 Mar 15. Essential oil of Perilla frutescens-induced change in hippocampal expression of brain-derived neurotrophic factor in chronic unpredictable mild stress in mice. Yi LT1, Li J, Geng D, Liu BB, Fu Y, Tu JQ, Liu Y, Weng LJ.
[xxxv] Neuroscience. 2002;112(4):803-14. A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning. Molteni R1, Barnard RJ, Ying Z, X et al.
[xxxvi]Ying Z, Roy RR, Edgerton VR, Gómez-Pinilla F. Exercise restores levels of neurotrophins and synaptic plasticity following spinal cord injury. Exp Neurol. 2005;193(2):411-9
[xxxvii] Eur J Appl Physiol. 2010 Sep;110(2):285-93. doi: 10.1007/s00421-010-1461-3. Epub 2010 May 14. Strength training does not influence serum brain-derived neurotrophic factor. Goekint M1, De Pauw K, Roelands B, Njemini R, Bautmans I, Mets T, Meeusen R.
[xxxviii] Sports Med. 2010 Sep 1;40(9):765-801. doi: 10.2165/11534530-000000000-00000. Neuroplasticity - exercise-induced response of peripheral brain-derived neurotrophic factor: a systematic review of experimental studies in human subjects. Knaepen K1, Goekint M, Heyman EM, Meeusen R.
[xxxix] J Clin Psychiatry. 2013 Nov;74(11):1076-83. doi: 10.4088/JCP.13m08413. Randomized placebo-controlled adjunctive study of an extract of withania somnifera for cognitive dysfunction in bipolar disorder. Chengappa KN1, Bowie CR, et. al.
[xl] Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3510-5. doi: 10.1073/pnas.1112209109. Epub 2012 Jan 30. Withania somnifera reverses Alzheimer's disease pathology by enhancing low-density lipoprotein receptor-related protein in liver. Sehgal N1, Gupta A, et.al.
[xli] Molecular Psychiatry (2007) 12, 1079–1088; doi:10.1038/sj.mp.4002075; published online 14 August 2007. Is it time to reassess the BDNF hypothesis of depression? J O Groves.
 
[i] Journal of Cerebral Blood Flow & Metabolism (2002) 22, 89–96; doi:10.1097/00004647-200201000-00011 Neuronal Plasticity and Dendritic Spines: Effect of Environmental Enrichment on Intact and Postischemic Rat Brain Supported by grants from the Swedish Medical Research Council (14X-4968) Swedish Brain Foundation, The Royal Swedish Academy of Sciences (12533), and the Russian RFFI (98–04–49550). Barbro B Johansson, Pavel V Belichenko
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Hi my name is Peter Smith I specialise in treating and coaching people how to live well with mental health problems, digestive health problems/IBS, sleep problems and type II diabetes using natural therapies.
I used these techniques to overcome and live well with my own bipolar disorder and IBS. I've been in practice as a natural medicine practitioner since 1988.
 

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