Sep
03
2016

Hidden Cause Of Depression

About 15.7 million Americans suffer from depression every year, but there remains a hidden cause of depression.

Not everybody responds well to antidepressant medicine. Only 30 to 50% of depressed people respond to antidepressants. There are two blood tests many physicians do not know and therefore fail to order: homocysteine blood levels and 5-methylfolate levels (5-MTHF).

Homocysteine as a hidden cause of depression

In 2004 a research group studied 924 middle-aged men. They noted that those men who fell into the highest third of homocysteine levels had a two-fold higher risk of being depressed than those who fell into the lower third of homocysteine levels. Other studies showed that SAMe, a nutrient that is required to build up mood enhancing neurotransmitters was sadly lacking in depressed people. In addition, folate levels were also found to be low in depressed people.

Having found this association between lack of nutrients and depression offered new opportunities to treat depression. Two studies examined the effect of taking 5-methylfolate on the effect of antidepressants. The result was astounding: in one study 7% of patients taking an antidepressant experienced improvement of their depression when assessed with a standard depression score. However, the same group improved their depression by 19% when 5-methylfolate was given in addition to the antidepressant.

Patients with the most severe depression on antidepressants had a 16% improvement of their depression. Adding 5-methylfolate to the antidepressant caused a 40% overall improvement in these severely depressed people, 24% more than without this simple vitamin supplement.

There is other evidence that patients with depression recover faster in the presence of 5-methylfolate. Moderately depressed patients recovered within 231 days on antidepressants alone, but in only 177 days when 5-methylfolate was present as well. The most severely depressed patients recovered within 150 days with antidepressants alone, but recovered within only 85 days on 5-methylfolate and the antidepressant.

Hidden cause of depression and Alzheimer’s disease

The story is getting more involved. Depression is related to proper balance of neurotransmitters that can be influenced by antidepressants and 5-methylfolate. But new research showed that Alzheimer’s disease (dementia) patients with cognitive decline have elevated homocysteine blood levels. A study in the New England Journal of medicine in 2002 found that after 8 years of observation more than 75% of them were diagnosed with Alzheimer’s disease. When blood homocysteine levels exceeded 14 micromole per liter the risk of Alzheimer’s had doubled compared to those with normal homocysteine levels. The researchers concluded that homocysteine is an important risk factor for the development of Alzheimer’s diseases and dementia, although it is not the only one.

Methylation pathway defects as a hidden cause of depression

40% of the population is defective in one or more genes that control the so-called methylation pathway in each of our cells (Ref. 1). This can slow down the metabolism of brain cells including the synthesis of certain neurotransmitters. At the same time it can cause the rising of homocysteine, which is then a useful marker for methylation defects. Another marker is the 5-methyl folate level, which, when low, indicates a deficiency in methyl donors including 5-methylfolate (5-MTHF).

Mental illness is an area where epigenetic factors play an important role. Depression that responds only partially or not at all to SSRI’s (antidepressants) often responds to L-methylfolate, a simple supplement from the health food store as a supplement. Similar epigenetic approaches are useful to treat psychosis, schizophrenia, bipolar disorder and Alzheimer’s disease.

Other illnesses due to methylation defects

Dr. Rozakis mentioned that 92% of migraine sufferers have a defective methylation pathway involving histamine overproduction and they can be helped with a histamine-restricted diet (Ref.2).

Autism, ADHD (hyperactivity) and learning disabilities are other diseases where methylation pathway defects are present. Physicians should check patients with autism for methylation pathway defects, and appropriate supplements and diet restrictions can help in normalizing the child’s metabolic defects. Mothers should consult with a DAN physician (“defeat autism now”) who is knowledgeable regarding all aspects of autism.

S-adenosylmethionine (SAMe) defects are another type of methylation defect, which associates with certain liver, colon and gastric cancers.

Dr. Rozakis went on to say that methylation defects lead to disbalances between T and B cells of the immune system and are important in autoimmune diseases like lupus or rheumatoid arthritis.

Methylation defects can also cause autoimmune thyroiditis and type 1 diabetes. They can also cause cardiac disease by raising homocysteine levels, which causes dysfunction of the lining of arteries and premature heart attacks.

Epigenetic factors through global methylation defects from vitamin B2, B6 and B12 deficiency can cause many different cancers. Hypomethylation is the most common DNA defect of cancer cells.

With skin diseases it has come to light that atopic dermatitis, eczema, psoriasis, scleroderma and vitiligo are related to methylation.

When we age, certain hormones are gradually missing, which leads to menopause and andropause. This leads to impaired cell function, elevated cholesterol, arthritis, constipation, depression, low sex drive, elevated blood pressure, insomnia, irritable bowel syndrome and fatigue. Replace the missing hormones with bioidentical ones, and symptoms will normalize.

Tests and treatment for hidden cause of depression

It is important for a physician to test patients for homocysteine levels once per year. As we age, we tend to lose some of the methylation pathway enzymes, which can result in an increase of homocysteine in the blood. A normal homocysteine level is less than 7 to 8 micromoles per liter. This is lower than the commonly recommended 15 micromoles per liter.

If the homocysteine level is too high, the treatment consists of methionine containing foods like dairy products and meat. Methionine, an essential amino acid, functions as a donor of methyl groups. The methyl groups normalize the methylation pathway defect and allow the homocysteine level in the blood to decrease. Research studies have been using 1000 to 5000 micrograms of 5-methyl folate daily to reduce homocysteine. Other B vitamins are necessary to reduce homocysteine, like vitamin B2, B6 and B12 in addition to 5-MTHF.

Hidden Cause Of Depression

Hidden Cause Of Depression

Conclusion

Depression and several other illnesses can be related to methylation pathway defects. This can cause a lack of 5-MTHF resulting in high homocysteine blood levels. It is important that a physician checks his elderly patients for homocysteine blood levels once per year. This will prevent depression, Alzheimer’s disease, migraines and a number of other illnesses.

Once a methylation pathway defect has been identified, it is relatively easy to treat the patient. The treatment consists of a proper methionine rich diet and 5-MTHF supplements as well as other B vitamins as discussed. It can prevent a lot of disability and human suffering.

References

Ref.1: William J. Walsh, PhD: “Nutrient Power. Heal your biochemistry and heal your brain”. Skyhorse Publishing, 2014.

Ref. 2: https://www.askdrray.com/life-expectancy-is-influenced-by-lifestyle/

Feb
08
2015

Preserve Your Memory

At the 22nd Annual A4M Las Vegas Conference in mid December 2014 Pamela Smith gave a presentation entitled ”How To Preserve Your Memory At Any Age”. She gave a comprehensive overview of what you can do to prevent Alzheimer’s disease. The better we understand the causes of Alzheimer’s the more we can interfere with the biochemical processes that lead to Alzheimer’s or dementia. Various parts of the brain have different functions like pattern recognition, interpreting auditory and visual stimuli and so on. In the past researchers thought that after the brain development it would be stationary until we die. But they have now shown that instead the brain continues to develop even after the teenage years. New brain cells can develop as long as we live and new synapses, the connections between brain cells can form all the time.

A lack of sleep causes insulin levels to rise, which causes a lack of memory. Alzheimer’s disease has been termed diabetes type 3 because of this close connection of memory loss and uncontrolled blood sugar levels. In fact diabetics are three times more likely to develop Alzheimer’s disease.

Subunits of the brain and neurotransmitters

There are several subunits of the brain like the hypothalamus, thalamus, hippocampus and the amygdalae, which are important for normal brain function and memory. The hippocampus in particular is a major memory-processing unit, which indexes, constructs and rearranges memories.

Apart from the anatomy of the brain, neurotransmitters are important for the proper functioning of the various parts. Although there are more than 100 of them the most important neurotransmitters are acetylcholine, GABA, glutamate, dopamine and serotonin. Each of these neurotransmitters binds to only one specific receptor before a neuron sends a signal to the next. There is a decline in the speed of neurotransmission with age and also a memory decline. Compared to the memory in a young person a person at the age of 75 has a decline in memory function of about 40%.

Why do people experience memory decline?

Apart from genetic predisposition the majority of people who come down with Alzheimer’s disease do so because of neglecting the body and their brain. Neglecting elevated blood pressure by not treating it properly with medication will lead to vascular dementia. As already mentioned earlier hyperinsulinemia (too much insulin in the blood) from obesity, untreated type 2 diabetes and metabolic syndrome is another mechanism.

There is an association of lack of exercise with a higher risk of developing Alzheimer’s, so is insomnia and a lack of sleep (less than 7 hours per night). With aging there is often poor nutrition, lack of absorption of nutrients, inflammatory bowel conditions with poor absorption of nutrients and body inflammation. A significant portion of the population is deficient for various enzymes in the methylation pathway, which can lead to high homocysteine levels and the danger of premature heart attacks and vascular dementia. Psychological health also affects memory loss, as do depression and anxiety. Toxins like heavy metals, fuels, pesticides, solvents and fluoride can over time lead to memory loss and Alzheimer’s as well.

Lifestyle habits and Alzheimer’s

There are many lifestyles that cause memory loss: too much stress (from high cortisol levels that damage the hippocampus); smoking that damages acetylcholine receptors; chronic alcohol abuse leads to memory problems from the toxic effect of alcohol on brain cells, which in turn causes a disbalance of serotonin, endorphins and acetylcholine in the hippocampus.

Lack of exercise is an independent risk factor for the development of Alzheimer’s disease. Exercise increases the blood supply of the brain, strengthens neural connections and leads to growth of neurons, the basic building blocks of the brain. Mood-regulating neurotransmitters are increased (serotonin, endorphins).

Sleep deprivation leads to memory loss, but so does the use of aspartame, the artificial sweetener of diet sodas.

Sugar consumption and too much pasta (which gets metabolized within 30 minutes into sugar) causes oxidization of LDL cholesterol and plaque formation of all the blood vessels including the ones going to the brain. On the long-term this causes memory loss due to a lack of nutrients and oxygen flowing into the brain.

Hormone changes

A lack of testosterone in men and estrogen in women interferes with cognition and memory. For this reason it is important after menopause and andropause (=the male menopause) to replace what is missing with the help of a knowledgeable health professional.

Too much DHEA from stress can decrease memory, but too little DHEA from aging can also do this. Alzheimer’s patients have DHEA levels that are 48% lower than men and women of the same age who have normal memories. Pregnenolone is a precursor of DHEA, estrogen, progesterone and testosterone. Dr. Smith called pregnenolone the “hormone of memory in the body”. At an age of 75 most people have a 65% lower level of pregnenolone than a persons in the mid 30’s. Pregnenolone keeps your brain balanced between excitation and inhibition, helps you to cope with stress and gives you energy.

Ask for input by hormone specialist

But before you consider supplementing with a pregnenolone hormone level, this should be ordered by a knowledgeable health professional. Dosing can be tricky as too much pregnenolone can result in too much DHEA, estrogen, progesterone or testosterone.

Progesterone is manufactured inside the brain, spinal cord and nerves from its precursor, pregnenolone, but in women it also comes from the ovaries until the point of menopause. Progesterone is needed in the production of the myelin sheaths of nerves and it has a neuroprotective function. In menopausal women bioidentical progesterone is a part of Alzheimer’s prevention.

Melatonin is a hormone, a powerful antioxidant and a neurotransmitter at the same time. It helps in the initiation of sleep, stimulates the immune system and protects from the toxic effects of cobalt, which has been found to be high in Alzheimer’s patients.

Other factors contributing to Alzheimer’s

Any inflammatory condition can trigger destruction of neurons, so do the beta-amyloid proteins associated with Alzheimer’s. Contributory factors can be food allergies, disbalance of gut bacteria, recreational drugs (particularly ecstasy) and certain medications. Dr. Smith stated that the most common foods causing allergies that affect the brain are: sugar, wheat, dairy, eggs, shellfish, potatoes, beef, tomatoes, corn, coffee, peanuts, roasted soy beans and yeast.

Dr. Smith mentioned that these medications can affect memory: statins, sedatives, steroids, levodopa, muscle relaxants; antihypertensive drugs, antidepressants, antibiotics, anticonvulsants, anti-arrhythmic drugs, pain relieving drugs (analgesics) and antihistamines. If you are on any of these, you may want to discuss alternatives with your doctor. Dr. Perlmutter mentioned in Ref. 1 that statins interfere with brain function and can lead to Alzheimer’s.

Promoting brain health

Medication helps only to stall further memory loss for up to 6 months, so Dr. Smith said about medications only: “much research is still needed in this area”.

On the other hand she stated that many foods, vitamins and supplements in combination could improve memory and prevent the development of Alzheimer’s disease. She spent considerable time in the remainder of her talk on details regarding foods, vitamins and supplements.

Dr. Smith said that we need to eat foods that are rich in antioxidants like blueberries, apples, raspberries, blackberries and strawberries; cherries, cranberries, cooked kale, garlic, grapes, prunes, raisins and raw spinach. But at the same time she stressed that we cannot trust the food industry anymore, and we need to buy organic foods. She gave an example of the “dirty dozen” as defined by the environmental working group (contaminated fruits and vegetables).

Food intake also applies to portions:eat 5 to 6 smaller meals per day. Consume red meat only three times per week.

The brain needs fats like nuts and seeds: walnuts, almonds, pine nuts etc.

Fish also contains healthy omega-3 fatty acids and DHA. The problem with predator fish like tuna or swordfish is that they are contaminated with mercury. But wild salmon and mackerel are still OK. A good alternative is to supplement with pharmaceutical grade EPA/DHA omega-3 capsules. They are molecularly distilled, which means they are not contaminated with mercury or PBC’s and they are more concentrated; they typically contain 1000 to 1400 mg of EPA/DHA per capsule. One to two capsules twice per day (a total of 2 to 4 per day) would be a good anti-inflammatory dose.

Specific food recommendations

Use olive oil and coconut oil for cooking; avoid the omega-6 oils (safflower oil, grape seed oil, sunflower oil, corn oil to just mention a few). These latter oils, which are heavily advertised by the food industry, create too much arachidonic acid leading to body inflammation. Your brain is very sensitive to inflammation, which causes Alzheimer’s. For the same reason avoid deep fried foods and processed foods.

There is more you need to watch for: no food additives, no artificial food colorings, no preservatives, flavors and MSG. Be alert about the food industry’s alternative “language” or terminology for MSG: “natural flavor”, “yeast extract” etc.

Preserve Your Memory

Preserve Your Memory

Brain nutrients

Dr. Smith reviewed a long list of brain nutrients that support the brain in its metabolism and prevent the development of dementia and Alzheimer’s disease.

I will only highlight the most effective and established nutrients here.

DHA: It has been known since 1999 that Alzheimer’s patients are missing DHA in their system. Molecularly distilled fish oil with high omega-3 fatty acids (both EPA and DHA) is one of the mainstays of prevention of inflammation in the body and the brain. 2 capsules twice per day of the concentrated 1000mg to 1400 mg capsules is desirable to prevent Alzheimer’s disease.

Phosphatylserine (PS): This phospholipid is part of the membrane of brain cells and controls what nutrients enter into them. It also increases the neurotransmitters acetylcholine, serotonin, norepinephrine, epinephrine and dopamine. Dr. Smith mentioned that PS is naturally present in foods like brown rice, fish, soy and green vegetables (particularly the leafy ones). The daily dosage recommended by Dr. Smith is 300 mg (note: some people develop a bothersome, but harmless bitter taste in the mouth at this dose; in this case take a lower dose like 100 or 200 mg per day).

Other supplements like Ginkgo biloba, alpha lipoic acid and others

Ginkgo Biloba: It improves blood flow to the brain and counteracts shrinkage of the hippocampus with age. Dr. Smith recommends 60 mg to 240 mg daily.

Alpha Lipoic Acid: Alpha lipoic acid is an antioxidant, helps stimulating the sprouting of new nerve cells and nerve fibers. Take 100 mg of alpha lipoic acid daily for memory.

Dr. Smith recommended many other supplements, which I will not explain in detail here: B vitamins, vitamin E and C, carnosine, acetyl-L-carnitine, boron, ginger, coenzyme Q-10 (or CoQ-10), curcumin, vinpocetine, zinc, grape seed extract, blueberry extract, Ashwaganda, glyceryl-phosphoryl-choline, SAMe, huperzine A and DMAE.

Dr. Smith discussed the benefits of CoQ-10 supplementation and reminded the audience that “whatever is good for the heart, is good for the brain”. She recommended to read Dr. Perlmutter’s book from which this phrase was borrowed (Ref. 1).

Genetic factors

Dr. Smith pointed out that there are about 5 genes that have been detected that are associated with Alzheimer’s disease and in addition the apolipoprotein E4 (APOE4). About 30% of people carry this gene, yet only about 10% get Alzheimer’s disease. This shows you how important lifestyle factors are. Physicians call this epigenetic factors. The can suppress the effect of the APOE4 gene. She also stated that our genes contribute only about 20% to the overall risk of developing Alzheimer’s disease. This leaves us with 80% of Alzheimer’s cases where we can use the brain nutrients discussed above and exercise to improve brain function.

Conclusion

Don’t wait for Big Pharma to develop a magic pill. Follow the simple steps in combination that Dr. Pamela Smith talked about in her presentation: Exercise, have organic food to keep toxins out of your body and brain, replace missing hormones with bioidentical ones and take supplements that are known to be effective (link for male menopause). In other words provide the right environment for your genes to work properly without getting Alzheimer’s disease.

Reference

1. David Perlmutter, MD: “Grain Brain. The Surprising Truth About Wheat, Carbs, And Sugar-Your Brain’s Silent Killers.” Little, Brown and Company, New York, 2013.

Oct
26
2013

Being SAD in Fall (Seasonal Affective Disorders)

Any general practitioner knows that fall and winter are the time when patients come in with a variety of complaints like a lack of energy, problems sleeping, inability to cope with stress, but often there may be non-specific pains like muscle spasm in the back, the shoulders, or indigestion. These symptoms can all be part of seasonal affective disorders (SAD) like depression, the winter blues, often coupled with anxiety.

Emotional health does not fit easily into our health care model. The receptionist will warn the doctor that this is going to be a “difficult” patient. If the doctor has only time for a 5 or 10-minute visit, where only one or two problems can be dealt with, then this does not fit when a patient with SAD has a problem concentrating, falling asleep, and presents with a long list of other complaints. Even 20 minutes or 30 minutes may not be enough to deal with this patient adequately. It is easier to send the patient for tests and to prescribe an antidepressant and a sleeping pill and reschedule for a follow-up appointment. But this likely will result in normal blood tests and investigations, added health care costs, but no solution to the patient’s problem when he  or she simply states “doctor, I feel so sick”.

I thought it would be interesting to review how our emotions can get out of balance and review an integrative approach to SAD.

Definition of SAD

Seasonal depression (also called seasonal affective disorder) occurs during fall (autumn) and winter, but this alternates with no depressive episodes during spring and summer. A person defined to suffer from SAD would have suffered from two major depressive episodes during the past 2 years with no depressive episodes in the intervening seasons of spring and summer (Ref.1). Alternative names for SAD are winter depression and wintertime blues. Typically SAD lasts about 5 months.

Brain hormone disbalance

Around 2002 it was detected that in mice there was a second light sensitive pathway from ganglion cells in the retina that were responsible for circadian hormone rhythms. This was later confirmed to be true also in humans, where photosensitive retinal ganglion cells buried deep in the retina and containing the pigment melanopsin absorb blue light in the visible light spectrum. The electrical signals are sent along the retinohypothalamic tract, so that light from the retina regulates the hormone circadian rhythm (daily hormone fluctuations including the sleep/wake cycle) in the hypothalamus. The hypothalamus is one of the major hormone centers in the center of the brain. As this publication shows there are minor genetic sequence changes for the retinal photopigment, melanopsin in patients with SAD. This affects about 1 to 2% of the American population. Many more have probably partial defects in the function of this pigment.

Being SAD in Fall (Seasonal Affective Disorders)

Being SAD in Fall (Seasonal Affective Disorders)

Many hormones in our brain experience a circadian rhythm.

When the sun goes down, melatonin is produced making us sleepy. In the morning serotonin production goes up and stays up all day, which normally prevents depression. There are other hormones that cycle during the course of the day. Cortisol is highest in the morning and low in the evening and at night. Growth hormone and prolactin are highest during sleep.

There is a lack of serotonin in the brains of patients with SAD and depression.

Symptoms of SAD

A person affected by SAD or any other patient with ordinary depression will present with symptoms of lack of energy, with tearfulness, negative thought patterns, sleep disturbances, lack of appetite and weight loss and possible suicidal thoughts. On the other hand symptoms may be more atypical presenting with irritability and overindulging in food with weight gain. Some patients somaticize as already mentioned in the beginning of this review experiencing a multitude of functional symptoms without any demonstrable underlying disease. It is estimated that up to 30 to 40% of patients attending a general practitioner’s office have some form of depression and in the fall and winter season a large percentage of them are due to SAD.

Treatment approaches to SAD

There are several natural approaches to SAD. However, before deciding to go this route, a psychiatrist should assess the patient to determine the risk for suicide. When a patient is not suicidal, light therapy can be utilized.

1. Light therapy: According to Ref. 2 a light box from Sun Box or Northern Light Technologies should be used for 30 minutes every morning during the fall and winter months. The box should emit at least 10,000 lux. Improvement can occur within 2 to 4 days of starting light therapy, but often takes up to 4 weeks to reach its full benefit (Ref.2).

2. Exercise reduces the amount of depression. The more exercise is done the less depression remains. A regular gym workout, dancing, walking, aerobics and involvement in sports are all useful.

3. Folate and vitamin B12: Up to 1/3 of depressed people have folate deficiency. Supplementation with 400 mcg to 1 mg of folic acid is recommended. Vitamin B12 should also be taken to not mask a B12 deficiency (Ref.3). Folate and vitamin B12 are methyl donors for several brain neuropeptides.

4. Vitamin D3 supplementation: A large Dutch study showed that a high percentage of depressed patients above the age of 65 were deficient for vitamin D3. Supplementation with vitamin D3 is recommended. (Ref.3). Take 3000 to 4000 IU per day, particularly during the winter time.

5. St. John’s Wort (Hypericum perforatum) has been found useful for minor to moderate depression. It is superior in terms of having fewer side effects than standard antidepressant therapy (Ref.3).

6. Standard antidepressants (bupropion, fluoxetine, sertraline and paroxetine) are the treatment of choice by psychiatrists and treating physicians when a faster onset of the antidepressant effect is needed (Ref.3).

7. Electro acupuncture has been shown in many studies to be effective in ameliorating the symptoms of depression and seems to work through the release of neurotransmitters in the brain (Ref.4).

8. A balanced nutrition (Mediterranean type diet) including multiple vitamins and supplements (particularly the vitamin B group and omega-3 fatty acids) also stabilize a person’s mood (Ref.3). Pay particular attention to hidden sugar intake, as sugar consumption is responsible for a lot of depression found in the general population.

9. Restore sleep deprivation by adding melatonin 3 to 6 mg at bedtime. This helps also to restore the circadian hormone rhythm.

Conclusion

Seasonal affective disorder is triggered by a lack of light exposure in a sensitive subpopulation. An integrative approach as described can reduce the amount of antidepressants that would have been used in the past in treating this condition. This will reduce the amount of side effects. The use of a light box can reduce the symptoms of this type of depression within a few days. But the addition of electro acupuncture and St. John’s Wort may be all that is required for treatment of many SAD cases. Regular exercise and a balanced nutrition (with no sugar) and including vitamin supplements complete this treatment. If the depression gets worse, seek the advice of a psychiatrist and make sure your doctor has ordered thyroid tests and hormone tests to rule out other causes where depression is merely a secondary symptom.

More information on depression: http://nethealthbook.com/mental-illness-mental-disorders/mood-disorders/depression/

References

  1. Ferri: Ferri’s Clinical Advisor 2014, 1st ed. © 2013 Mosby.
  2. Cleveland Clinic: Current Clinical Medicine, 2nd ed. © 2010 Saunders.
  3. Rakel: Integrative Medicine, 3rd ed. © 2012 Saunders.
  4. George A. Ulett, M.D., Ph.D. and SongPing Han, B.M., Ph.D.: “The Biology of Acupuncture”, copyright 2002, Warren H. Green Inc., Saint Louis, Missouri, 63132 USA

Last edited Nov. 7, 2014