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I think this physician is too extreme but for sure you need a balance between antioxidants and oxidant and oxidant are very important to kill virus, bacteria, inflammation….
It’s an example:
If you have optimal hormonal and immune pathways with optimal diet and exercise level and you become to be old, what the best way to improve/protect brain dopamine pathway ? Each decade you lose dopamine level, I don’t known why ?
– may be because there are an increase MAOb ( because you lose your sex hormone level)
– because nitrostress or oxydatif stress increase
– because low grade inflammation increase(infection, leaky gut, dysbiosis…)
– because there are more glycosylation
– because thyroïde, GH, IGF-1 decrease
– it’s only aging (telomere, mitochondriopathy …)I think that a good dopamine pathway, particulary in the prefrontal cortex, is very important to preserve/improve with aging.
I known that exercise, good diet, brain training is the key. But with aging, do you think that some medication like selegiline (IMAOb), modafinil, low dose of valproic acid, metformin, low dose of dexedrine or ritalin, some nicotine gum or pacth have some value or not ?
Scharzenenerger and Eastwood smoke sometime a good cigar, maybe there are some value for the hormesis effect.
Thanks you for this good analysis, many publications have financial interest and have some biased answer. I like the answer of 2 scoops of milk protein powder. 🙂
OUPS. Dr Mariano, I should like to have the same brain prefrontal cortex of you.
This post is amazing.
Best regards.@Jean 6723 wrote:
Also a nice study about gut microbia and diabetes
@Jean 6716 wrote:
Thank Dr Mariano.
Two more theory about diabetes type 2 is the “leaky gut”, HCSF (high frucose corn syrup increase methylglyoxal and POP (many pollutants cause insulin resistance@DrMariano 6701 wrote:
One of the biggest problems in medicine is that when one has a complex illness, often only one underlying cause of the illness is addressed – and often with only a medication treatment.
One example is diabetes type 2. Diabetes is a complex illness often involving:
1. insulin resistance – resulting in blood sugar control problems and excessive insulin signaling (until the pancreas beta-cells are destroyed).
2. suboptimal thyroid signaling
3. excessive pro-inflammatory signaling with an activated immune system
4. an overactive sympathetic nervous system – which increases insulin resistance
5. nutritional deficiencies – such as vitamin D deficiency, along with other animal fat associated nutrients.
6. hypogonadism
7. obesity – and its attendant ramifications
8. dyslipidemia and cardiovascular problems including hypertension
9. mental impairment/illness/nervous system dysfunction – with an increased risk for dementia, mood disordersAddressing blood sugar control alone will not be adequate to limit the damage that results from diabetes (that result in complications from diabetes including blindness, heart disease, kidney failure, stroke, and eventually an early death). Each identifiable underlying factor needs to be addressed. These underlying factors are the pathophysiology of the illness.
Until the pathophysiology of an illness is well-described, treatment is trial and error and mostly error.
When it comes to mental illness, such as ADHD, the biggest problem is that too often, the pathophysiology is never identified by the treating practitioner prior to treatment.
DSM-IV is only a description of the illness. It does not identify the pathophysiology underlying the illness. It is insufficient to determine the treatment an individual patient needs.
When it comes to ADHD, the most common underlying problems I find are:
1. nutritional deficiencies
2. suboptimal thyroid signaling
3. excessive pro-inflammatory signaling – such as from autoimmune problems, inappropriate production of antibodies against foods, an overactive immune system.
4. suboptimal nervous system dopamine signaling
5. excessive norepinephrine signaling – which over time may result in hypothalamic-pituitary-adrenal axis dysregulation and mood problems common in ADHDEach of the underlying pathophysiologies can impair attention, memory, and information processing as found in ADHD. Each can influence the other pathophysiologies.
Each of the underlying pathophysiologies can be considered a separate illness in its own right. But like diabetes, the sum of them is the illness of ADHD. ADHD or mental illness can be considered the umbrella diagnosis overlying multi-system problems.
Stimulants are the single most effective treatment for ADHD. Clearly. But they do not work all the time, particularly if there is HPA Axis dysregulation and/or excessive pro-inflammatory signaling. The increase in norepinephrine signaling from a stimulant may worsen these underlying factors, thus negating the benefit of the stimulant.
Addressing the underlying factors generally reduces the need or dose for stimulants, particularly if the effects summate to an optimal dopamine signaling state and nervous system metabolism. For example, if you can make dopamine yourself, why would you need a stimulant to raise levels? You may not need it when production is corrected.
If the other underlying factors are not addressed in treatment, then stimulant treatment does pose a risk. For example, once HPA-Axis dysregulation occurs, then one may not be able to control the inflammation or norepinephrine signaling that increases with stimulant treatment.
The article has a lot of inaccuracy. For example, it classifies Lithium oratate as a non-pharmaceutical treatment. It is a medicinal and thus pharmaceutical treatment. Lithium is not an essential nutrient in the body. Pharmaceutical lithium is not poorly absorbed into the brain. It is used in high doses because it is a medicinal treatment for bipolar disorder where there are therapeutic blood levels that need to be achieved. Amino acid treatments which are not addressing a nutritional deficiency, to me, are medicinal treatments. The use of a cholinesterase inhibitor is not useful in ADHD. It reduces dopamine production (which is why depression, mental impairment and suicidal behavior may occur particularly if there is no demonstrated acetylcholine signaling problem as in Alzheimer’s disease). Piracetam is a treatment I would never use in children. It doesn’t work well either. Nor is its mechanism of action clear – thus making the treatment roll of the dice. Most of the treatments described rely on statistics to demonstrate efficacy rather than identifying a pathology to target. Thus, from my point of view, they are all used medicinally/pharmacologically. The value of the article is that it does encourage practitioners to look for underlying factors though he calls each underlying factor a separate illness rather than a part of ADHD.
Thank Dr Mariano.
Two more theory about diabetes type 2 is the “leaky gut”, HCSF and POP. Many pollutants cause insulin resistance@hardasnails1973 4982 wrote:
This is why you support the proper neurotransmitters with the proper precursors. Drugs have their place in medicine for sure. I prefer to use an intergrative approach with Drs by looking at the factors which are causing the issue in the first place. If you are not willing to commit to a dietary and lifestyle change, then you are not committed to getting well. The power of proper eating is so over looked it scary. The results I have seen just through slight dietary and little nutritional support in some instance out weight response to harsh drugs. You need to look towards motive. Dr Hyman is all about marketing. Its $1500 just to walk in the door to see him and then you get blasted with few $1,000 in blood test. By doing this you create a bad reputation. Dr OZ has fallen into this trap and medical professionals begin to lose respect for these people. I have several clients who have gone to Rothernberg, hyman, Gordon, ect only ending up with and an empty wallet. Its all about marketing. I prefer the silent, but humble approach works better. Other medical professionals will give you much desired respect.
Nice answer Hardasnails. But do you practice the same medicine of Jeffrey Bland, Dr Hyman, ect…. without the marketing of this doctors ?
This is a problem today because there are many informations and misinformation’s and many physicians have a simplest solution. I like your vision because I known if it’s the true. But the difficulty today is that doctor are not formed for this holistic vison
Dr Mariano what do you think about functional medecine ? This is a new vogue a mediatic physician like Dr Hyman. It’s interesting because there are more physiological comprehension of disease.
But but I don’t like the star system and show of this doctor. Some doctor like Dr Hyman have a big interest of supplement company and give a bad opinion about antidepressant drug.
I think in medecine there are not black and white, conspiracy Big pharma or the panacea of nutrition and supplement.This is a problem today because there are many informations and misinformation’s.
Dr Mariano what do you think about functional medecine ? This is a new vogue a mediatic physician like Dr Hyman
@DrMariano 4945 wrote:
The problem with using imaging studies such as PET scans and functional MRI is that they actually do not demonstrate that the overactive circuit is the only circuit involved or is even the central circuit involved in causing the mental problem.
For example, the circuits which are overactive may actually be instead compensating for underactivity in other circuits. But no one talks about these underactive circuits since they don’t light up like pretty Christmas lights on the scan.
The whole brain is affected by depression – including the overactive and underactive circuits.
In fact his is very complex story and study doesn’t reveal everything. Thank
@compaq 4886 wrote:
What to take from this?
Amphetamines might be bad for our brains?
. Amphetamine massively down regulates VMAT2 which has all sorts of effects from Parkinson’s disease to depression, both which have been shown to occur at alarming rates in amphetamine users. Ritalin doesn’t down regulate VMAT2 but up regulate it
The low dose of amphetamine is less likely to have side effect on the brain, but anybody known after long period of low dose of amphetamine is a really bad or not.
With that said, lithium has been shown to up-regulate VMAT2 as well as D2/D3 autoreceptors (which are important in combating dopamine dysregulation). There is also reason to believe that increased VMAT2 could help prevent amphetamine induced neurotoxicity, though much of the research I’m quoting used rat studies.
the VMAT2-deficient mice show Parkinson’s-like pathology, marked neurodegeneration, and anxiety/depressive-like behavior. Note, importantly, that a main part of amphetamine’s mechanism of action is VMAT2 inhibition and other psychostimulants (e.g. methylphenidate, modafinil) do not share amphetamine’s VMAT2 inhibition.
other studies looking at VMAT2 inhibition suggest that it results in progressive damage due to a lack of DA sequestration.
Parkinsons Dis. 2011 Feb 21;2011:124165.
VMAT2-Deficient Mice Display Nigral and Extranigral Pathology and Motor and Nonmotor Symptoms of Parkinson’s Disease.
Taylor TN, Caudle WM, Miller GW.
Department of Environmental Health, Rollins School of Public Health, Emory University, 1518 Clifton Road, Atlanta, GA 30322, USA.
Abstract
Dopamine is transported into synaptic vesicles by the vesicular monoamine transporter (VMAT2; SLC18A2). Disruption of dopamine storage has been hypothesized to damage the dopamine neurons that are lost in Parkinson’s disease. By disrupting vesicular storage of dopamine and other monoamines, we have created a progressive mouse model of PD that exhibits catecholamine neuron loss in the substantia nigra pars compacta and locus coeruleus and motor and nonmotor symptoms. With a 95% reduction in VMAT2 expression, VMAT2-deficient animals have decreased motor function, progressive deficits in olfactory discrimination, shorter latency to behavioral signs of sleep, delayed gastric emptying, anxiety-like behaviors at younger ages, and a progressive depressive-like phenotype. Pathologically, the VMAT2-deficient mice display progressive neurodegeneration in the substantia nigra (SNpc), locus coeruleus (LC), and dorsal raphe (DR) coupled with α-synuclein accumulation. Taken together, these studies demonstrate that reduced vesicular storage of monoamines and the resulting disruption of the cytosolic environment may play a role in the pathogenesis of parkinsonian symptoms and neurodegeneration. The multisystem nature of the VMAT2-deficient mice may be useful in developing therapeutic strategies that go beyond the dopamine system.
