Info regarding depression

[triffid113]

I found this article of interest...I know there have been several others over time who wanted to know what supplements were required to make serotonin, and I thought I'd post this info pointing to one supplement I was unaware affects serotonin and dopamine levels. The paper is accessible at the link should you care to read it:

(Note: I read PLP as P5P, which is active B6)
http://discovery.ucl.ac.uk/1310134/

The neurochemical consequences of aromatic L-amino acid decarboxylase deficiency
Allen, G.F.G. (2011) The neurochemical consequences of aromatic L-amino acid decarboxylase deficiency. Doctoral thesis, UCL (University College London).
Aromatic L-amino acid decarboxylase (AADC) catalyses the conversion of 5-hydroxytryptophan (5-HTP) and L-3,4-dihydroxyphenylalanine (L-dopa) to the neurotransmitters serotonin and dopamine respectively. The inherited disorder AADC deficiency leads to a severe deficit of serotonin and dopamine as well as an accumulation of 5-HTP and L-dopa. This thesis investigated the potential role of 5-HTP/L-dopa accumulation in the pathogenesis of AADC deficiency. Treatment of human neuroblastoma cells with L-dopa or dopamine was found to increase intracellular levels of the antioxidant reduced glutathione (GSH). However inhibiting AADC prevented the GSH increase induced by L-dopa. Furthermore dopamine but not L-dopa, increased GSH release from human astrocytoma cells, which do not express AADC activity. GSH release is the first stage of GSH trafficking from astrocytes to neurons. This data indicates dopamine may play a role in controlling brain GSH levels and consequently antioxidant status. The inability of L-dopa to influence GSH concentrations in the absence of AADC or with AADC inhibited indicates GSH trafficking/metabolism may be compromised in AADC deficiency. 5-HTP was demonstrated to potentially be mildly toxic to human neuroblastoma cells but not astrocytoma cells; however the concentrations required for this response are likely to be higher than pathophysiological levels in AADC deficiency. These results indicate the need for investigations addressing the effects of chronic 5-HTP exposure as only acute effects were investigated in the current study. This thesis also investigated the effect of altered availability of the AADC coenzyme pyridoxal 5‟-phosphate (PLP) on AADC activity, protein and expression. In two patients with inherited disorders of PLP metabolism reductions in plasma AADC activity were observed. Furthermore PLP-deficient human neuroblastoma cells were found to exhibit reduced levels of AADC activity and protein but not altered expression. These findings suggest maintaining adequate PLP availability may be important for optimal treatment of AADC deficiency.

 

[triffid113]

Also found a few interesting bits in this article: http://www.biogaba.com/images/nutrients_botanicals_stress.pdf

Ashwaganda counteracts biological changes related to stress including blood sugar changes, adrenal weight, cortisol production. One animal study showed it prevented depression and anxiety-associated behavior caused by social isolation. [I have not found it to work for me though]

Rhodiola affects levels of dopamine, serotonin, and norepinephrin in the brain. (Possibly it is a MOA inhibitor. I am alreadt COMT +/+ so I doubt this mechanism has any effect in me but if you are not COMT +/+ I believe this herb is a COMT inhibitor). It prevents depletion of adrenal catecholamines. It may activate opiod receptors. It reduces adrenalin-induced arrythmias (in me it caused a 1/day arrythmia of SLOWED heart rate). One study in humans showed it reduced anxiety significantly at a dose of 50mg 2x/day. Another study in humans showed decreased stress-related fatigue and less stress-raising of cortisol at a divided dose of 576 mg. Physicians studied taking rhodiola when starting night duty experienced less fatigue and improved mental performance. Students studied taking 50mg 2x/day found less mental fatigue and better mood stability. It also increased exam scores. Other studies found it helps the heart. [Rhodoila works for me FANTASTICally! I used to call in 'Mother's Little Helper'. It made me not care about stress (deadlines), like water off my back, it prevented low blood sugar attacks due to stress, and it made me HAPPY. However due to the arrythmia it caused me, I only take it when I am having low blood sugar issues, and I take it for about a month until the issues go away until next time. I later found Olive Leaf Extract would cancel out the arrythmia caused by the rhodiola but I am on so many pills now that I still take this only as needed.]

The article also talks about the various ginsengs but I don't take those. They affect your hormones and I need something stronger -- DHEA, so I do not want to play with my hormones with multiple products at cross-purposes. (I think I tried ginseng and it messed with what the DHEA does for me so I quit it).

PS apparently blunts the adrenal response to stress. That is a new one on me, but interesting.

Quite a lot of other herbals and nutrients for stress are discussed. The article is too long to summarize but check it out if you have an interest.

 

[heapsreal]

i have found p5p with tryptophan helps sleep some and mood is good the next day. i have found tryptophan to be better then 5htp but thats just my experience.
phosphatidylserine/PS i have read improves cortisol sensitivity, so apparently helps one if they over respond to cortisol?? But it looks like one has to be careful if cortisol is low. I think problems arise with people who dont make enough cortisol in the morning so are tired but then make just alittle too much at night so cant sleep, we need to lower night time cortisol without affecting morning cortisol?? Its a tough balance to get right. Im increasing my morning cortisol with pregnenolone and then the PS at night to lower it. it seems that our body has lost the ability to regulates this hormone pattern so we need to regulate it ourselves??

 

[triffid113]

I have a file of info on thyroid and in it I found this (no link unfortunately but clearly it is from Life Extension. I included the entire list for completeness, but the 1st 3 ticks are of special interest for people here...the second and third are in regards to depression...I also frequently experience that "slowed mental processes" which is NOT the same as being stoopid. Also many other sources have stated that brain fog can be (or possibly ALWAYS IS caused by thyroid imbalance). Most people think they do not have a thyroid issue based on their TSH falling right in the middle of the "standard reference range" posted by the lab. But as this range is NOT based on science, that is patently FALSE. Right in the middle of the standard reference range means you are HYPOthroid! Anyway, below Life Extension says gastrointestinal issues and depression can be caused by hypothyroid:

Consequences of Hypothyroidism
· Gastrointestinal problems: Hypothyroidism is a common cause of constipation. Constipation in hypothyroidism may result from diminished motility of the intestines. In some cases, this can lead to intestinal obstruction or abnormal enlargement of the colon.36 Hypothyroidism is also associated with decreased motility in the esophagus, which causes difficulty swallowing, heartburn, indigestion, nausea, or vomiting. Abdominal discomfort, flatulence, and bloating occur in those with small intestinal bacterial growth secondary to poor digestion.31

· Depression and psychiatric disorders: Panic disorders, depression, and changes in cognition are frequently associated with thyroid disorders.37 Hypothyroidism is often misdiagnosed as depression.38 A study published in 2002 suggests that that thyroid function is especially important for bipolar patients: “Our results suggest that nearly three-quarters of patients with bipolar disorder have a thyroid profile that may be suboptimal for antidepressant response.” 39

· Cognitive decline: Patients with low thyroid function can suffer from slowed thinking, delayed processing of information, difficulty recalling names, etc.40 Patients with subclinical hypothyroidism show signs of decreased working memory,41 and decreased speed of sensory and cognitive processing.42 An evaluation of thyroid hormones along with TSH may help avoid misdiagnosis as being depressed. 43

· Cardiovascular Disease: Hypothyroidism and subclinical hypothyroidism are associated with increased levels of blood cholesterol, increased blood pressure, and increased risk of cardiovascular disease. 44 Even those with subclinical hypothyroidism were almost 3.4 times as likely to develop cardiovascular disease than those with healthy thyroid function.45

• • High blood pressure: Hypertension is relatively common among patients with hypothyroidism. In a 1983 study, 14.8% of patients with hypothyroidism had high blood pressure, compared with 5.5% of patients with normal thyroid function. 46“Hypothyroidism has been recognized as a cause of secondary hypertension. Previous studies … have demonstrated elevated blood pressure values. Increased peripheral vascular resistance and low cardiac output has been suggested to be the possible link between hypothyroidism and diastolic hypertension.”47
  • High cholesterol and atherosclerosis:“Overt hypothyroidism is characterized by hypercholesterolemia and a marked increase in low-density lipoproteins (LDL) and apolipoprotein B”48 These changes accelerate atherosclerosis, which causes coronary artery disease.43 The risk of heart disease increases proportionally with increasing TSH, even in subclinical hypothyroidism.49 Hypothyroidism that is caused by autoimmune reactions is associated with stiffening of the blood vessels. 50 Thyroid hormone replacement may slow the progression of coronary heart disease by inhibiting the progression of plaques.51,52
  • Homocysteine: Treating hypothyroid patients with thyroid hormone replacement might attenuate homocysteine levels, an independent risk factor for cardiovascular disease: “A strong inverse relationship between homocysteine and free thyroid hormones confirms the effect of thyroid hormones on homocysteine metabolism.”53
  • Elevated C-reactive protein: Overt and subclinical hypothyroidism are both associated with increased levels of low-grade inflammation, as indicated by elevated C-reactive protein (CRP). A 2003 clinic study observed that CRP values increased with progressive thyroid failure and suggested it may count as an additional risk factor for the development of coronary heart disease in hypothyroid patients. 54

o Metabolic Syndrome: In a study of more than 1,500 subjects, researchers found that those with metabolic syndrome had statistically significantly higher TSH levels (meaning lower thyroid hormone output) than healthy control subjects. Subclinical hypothyroidism was also correlated with elevated triglyceride levels and increased blood pressure. Slight increases in TSH may put people at higher risk for metabolic syndrome. 55

· Reproductive system problems: In women, hypothyroidism is associated with menstrual irregularities and infertility.56 Proper treatment can restore a normal menstrual cycle and improve fertility. 57

· Fatigue and weakness: The well known and common symptoms of hypothyroidism, such as chilliness, weight gain, paresthesia (tingling or crawling sensation in the skin) and cramps are often absent in elderly patients compared with younger patients, fatigue and weakness are common in hypothyroid patients.58
Life Extension suggests an optimal level of TSH between 1.0 and 2.0 mIU/L, as some studies have noted that a TSH above 2.0 may be associated with adverse cardiovascular risk factors. 26 In addition, a TSH between 1.0 and 2.0mIU/L has been associated with the lowest subsequent incidence of abnormal thyroid function.66
People who avoid iodized salt or adhere to a salt-restricted diet may become iodine deficient.112 Vegetarians are also at risk of developing iodine deficiency, especially if they eat food grown in low iodine soil.113 Vegans that avoid sea vegetables, are also at higher risk.114

Diets both low and high in iodine are associated with hypothyroidism. This is supported by studies that have shown that both low and high urinary iodine excretion are associated with hypothyroidism.115 High intake of iodine also increases the risk of Hashimoto’s thyroiditis.116
...

According to a study reported in Lancet, various TSH levels that fall within normal range are associated with adverse health outcomes.26
· TSH greater than 2.0: increased 20-year risk of hypothyroidism and increased risk of thyroid autoimmune disease
· TSH between 2.0 and 4.0: hypercholesterolemia and cholesterol levels decline in response to T4 therapy
· TSH greater than 4.0: greater risk of heart disease
[Summary, your TSH should be BELOW 2.0]

 

[triffid113]

i have found p5p with tryptophan helps sleep some and mood is good the next day. i have found tryptophan to be better then 5htp but thats just my experience.
phosphatidylserine/PS i have read improves cortisol sensitivity, so apparently helps one if they over respond to cortisol?? But it looks like one has to be careful if cortisol is low. I think problems arise with people who dont make enough cortisol in the morning so are tired but then make just alittle too much at night so cant sleep, we need to lower night time cortisol without affecting morning cortisol?? Its a tough balance to get right. Im increasing my morning cortisol with pregnenolone and then the PS at night to lower it. it seems that our body has lost the ability to regulates this hormone pattern so we need to regulate it ourselves??

Good info, Heaps. Interesting to note you have tried P5P + tryptophan and found it to work as the study indicated. I get NO result from 5-HTP, but I have no trouble sleeping. I believe there is some other mechanism for sleeping besides melatonin -- I read a reference once - I have the book, I'll have to check. But some other hormone - messed up in the case of allergics - also causes no difficulty sleeping. I started taking melatonin because I read it is one of the BEST antioxidants for the brain (next to dopamine), and I find taking melatonin at night (I take 6mg) makes me feel more peaceful the next day. At one time studies showed melatonin helps depression. I have not seen that in myself but I feel VERY CLEARLY more peaceful, which a lifelong goal of mine.

 

[heapsreal]

definately other issues with sleep other then melatonin, i also use melatonin as it said to be a great antioxidant. I think the ps has helped me with sleep by lowering high night time cortisol

 

[triffid113]

I'll have to look up PS. It's never been on my radar. Thanx