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Hit or Miss Supplements for Depression

By Jurriaan Plesman, BA(Psych), Post Grad Dip Clin Nutr

Depression is a serious illness and should always be treated by proper qualified health practitioners.
The quest for alternatives medication for depression stems directly from the general dissatisfaction of drug therapy. Antidepressant drugs are beneficial to about 40% of patients, according to some studies I have read. This leaves 60% with treatment resistant depression. The fact that psychiatrists prescribe drugs indicate that we are dealing with a physical abnormality in the brain. If this were true then it would be a contradiction to say that PSYCHOTHERAPY will help overcome depression. No amount of talk therapy can overcome a PHYSICAL disease. You don’t treat diabetes with psychotherapy. But leaving psychotherapy on one side for the time being, let us look at physical remedies.

Most approaches that involve drugs such as SSRIs or even natural supplements such as St John’s Wort, SAM-E, 5-HTP, are really “hit or miss” remedies.Most of these remedies target biochemical abnormalities in the brain that can be responsible for depression. They help to increase biochemical END PRODUCTS.
For example, most SSRIs (antidepressant drugs for which we have a brand name for every letter of the alphabet) inhibit the reuptake of serotonin, the ‘feel-good’ neurotransmitter thereby increasing the amounts of serotonin and possibly other neurochemicals. However, there are several studies to show that treatment with anti-deperssant medications may leave many patients with “treatment resistant depression”. See here.

St John’s Wort produces its antidepressant effect by the same mechanism, but in milder form. It is reported to be beneficial not only in depression, but also in anxiety and premenstrual syndrome (PMS), fibromyalgia and has pain relieving effects. It is also used in insomnia and when depression is marked by fatigue, sleepiness, and low energy levels. It also aids in the ‘winter blues’ or ‘seasonal affective disorder’ (SAD), a mood disorder associated with shorter days and longer nights of autumn and winter. SAD may be accompanied by increased consumption of carbohydrates and gaining weight. Like a prescription drug, the St John’s Wort needs to build up over some time to become effective. It should NOT be taken with antidepressant drugs as these may interact, as well as with some other drugs, especially blood thinning drugs. .Although side effects are uncommon, these may include constipation, upset stomach, fatigue, dry mouth and dizziness. Also, people should avoid extended periods in sunlight as it may increase sensitivity to the sun.

The latest derivative from St John’s Wort is hyperforin, a component of the plant that has been isolated.  Some medical studies have claimed that it can be an effective antidepressant supplement. Search the Internet for AMORYN.

The interdependence of nutrients

The cardinal rule in nutritional therapy is that nutrients work in co-operation with other nutrients. Vitamin B3 (niacin) deficiency can cause depression because in that case the body will use up all the tryptophan (forerunner of serotonin) to manufacture vitamin B3 (at the rate of 60 to 1), leaving little tryptophan for conversion to serotonin. Since serotonin is also the forerunner of melatonin, this will affect our sleeping patterns. Now, low tryptophan levels can also cause a zinc deficiency, because the absorption of zinc – an important coenzyme in about 80 or more enzymes – requires its binding with picolinic acid for transport across the membranes of the gut. Picolinic acid is produced in the pancreas from tryptophan under the influence of vitamin B6!!
Vitamin B6 is essential in the conversion of tryptophan to serotonin, but this vitamin is also dependent on the presence of zinc. Vitamin B6 (pyridoxine) needs to be converted to an active form called pyridoxal-5-phosphate (P5P) (or PLP), by a zinc containing enzymes – pyridoxine kinase. Riboflavin is required both to convert (a) tryptophan into niacin and (b) pyridoxine (B6) into its active form P5P. (McCormick DB, (1989)  This interdependence also applies to many other nutrients, and this is one reason why supplements from natural sources are sometime more effective. Zinc deficiency leads to an imbalance of the zinc/copper ratio and may lead to Cerebral Hypoglycia (Type 6, Hypoglycemia), although actual blood sugar levels are within normal range.
Thus as noted, conversion of tryptophan into serotonin requires sufficient amounts of vitamin B6 (pyridoxine) zinc, Vitamin D (sun) and magnesium and many more. Thus if there is a deficiency of these nutrients, then one possible result is depression. Vitamin B6 is involved also with detoxification. Thus if a person is using drugs – any xenobiotic drug or pollution or toxin – then the body may lack one of the coenzymes in the production of serotonin. One of the signs of B6 deficiency is reported to be lack of dream recall. EbbenM et als, (2002)

SAM-e (S-Adenosyl-Methionine) is a good and well-researched antidepressant natural remedy. It is found in all body cells and is produced from methionine (found in high protein food sources) and folic acid, Vitamin B12 and trimethylglycine (betaine from choline). It plays an important role in methylation, a chemical reaction in which a methyl group is donated to another molecule, thereby changing its shape and function. It affects several physical processes, including the regulation of some hormones and the neurotransmitters serotonin, melatonin, dopamine and adrenaline (important regulators of mood). SAM-e alters the shape and actions of other chemical molecules by donating its methyl group (CH3). Werbach, 143  It has a reputation of being a very effective antidepressant – as well as other health benefits – without any side effects.

SAM-e is formed from methionine in combination with Adenosine Triphosphate (ATP), thus

methionine + ATP = SAM-e

Since ATP is the molecule of energy derived from glucose metabolism, people with insulin resistance (hypoglycemia) will have problems producing adequate amounts of SAM-e, which could be responsible for depression and mental illness. Once SAM-e has donated its methyl group (CH3) it becomes homocysteine – a substance that in excess has been associated with heart disease. Homocysteine can be converted to glutathione via a B6 dependent enzyme (an antioxidant), or back to methionine with the help of vitamin B12 and folic acid.

Hence an affordable way of increasing SAM-e, would be by supplementing with methyl-enhancers, such as vitamin B12, folic acid, vitamin B6, anhydrous betaine-TMG. See also methyl donor.

5-HTP (5-Hydroxytryptophan) is derived from tryptophan and is the immediate forerunner of serotonin. Unlike the supplement of tryptophan it can be taken any time. Tryptophan has to compete with other amino acids before absorption. Again vitamin B6 is required for its conversion to serotonin and melatonin.

DHEA (Dehydroepiandrosterone), an androgen produced in the adrenal cortex, is one of the very popular supplemental hormones often associated with aging problems. It is the most prevalent hormone in your body and over a life time is probably twenty times more abundant than any other hormone in production. It is regarded as a building block hormone, because it is used by different organs. It not only strengthens muscles, keeps mucous membranes moist, boosts immunity and jack up the libido but also fights depression, anxiety and promotes a sense of well being and it improves memory. It is also a balancing hormone of other hormones such as cortisol. Hence this is another supplement used in the fight against depression.

L-Phenylalanine (Phe) together with vitamin B6 starting with 500mg can be decarboxylated to phenylethylamine (PEA), also found in chocolate, and may relieve depression and also in bipolar disorder. Phe is the forerunner of dopamine and norepinephrine, low levels of which may lead to depression. This supplement should be given under medical supervision, because its side effects increase anxiety in some people. It may increase blood pressure and this supplement should not be used in people with PKU (phenylketonuria) or pre-existing pigmented melanoma, a type of cancer.

Now although I prefer natural remedies to synthetic artificial drugs – as an initial trial in treatment – it is unfortunate that psychiatrists are reluctant to prescribe them, because they may be accused of ‘unproven medical practice’ or ‘unconventional medicine’ and threatened with medical deregistration. Besides these natural remedies cannot be patented, and cannot be monopolized by pharmaceutical companies, and this is where economics and politics enters the game of ‘psychiatry’. Mainstream medicine is not prepared to spend R&D moneys to show that natural remedies are “unproven medical practice”.
The biggest draw back to natural remedies is their price, which leaves most of them out of reach of ordinary people.

The reason why I consider these remedies – both drugs and natural – “hit or miss” remedies, is because they may miss the targeted biochemical imbalance thought to be responsible for depression. SSRIs or natural remedies may not overcome the deficiencies of vitamin B3, B6, B12, folic acid, magnesium, and a host of other deficiencies or nutritional imbalances such as riboflavin, biotin, thiamine (B1), vitamin C, calcium, copper, iron, lithium, potassium, or vanadium toxicity, omega-3 and -6 fatty acids, all known to affect depression. See Werbach (Chapter on Depression page 123)

Furthermore, all these remedies overlook other metabolic conditions that are known to be responsible for depression, such as insulin resistance (hypoglycemia). Studies have shown that there is a significant association between depression and insulin resistance. See “Depression and Insulin resistance” at our web site. Nor does it take into account a plethora of physical diseases that are known to be responsible for depression, such as hypothyroidism (Type 4, Hypoglycemia), subclinical Coeliac Disease, Fibromyalgia, Crohn’s Disease, Ulcerative Colitis, even arthritis and a host of other degenerative diseases. See: Diseases Associated with Depression and Silent Diseases and Mood disorders.

Yet, if this sounds all very depressing the nutritional treatment for depression is in everybody’s reach.
Instead of buying natural remedies or drugs, that aim at producing biological END PRODUCT for neurotransmitters in the brain, you can go on a high protein diet, plus the various nutritional supplements such as vitamin C, zinc, chromium picolinate, B-complex vitamins, omega-6 & -3 fatty acids and lecithin, helping your body to build these END PRODUCTS. The hypoglycemic diet, adjusted to the individual needs of the person is the ideal nutritional diet for mentally ill people.

Nutritional therapy is just not ‘good nutrition’, it is a special nutritional technique for stabilizing blood sugar levels, thereby normalizing adrenaline and cortisol levels,. These stress hormones are among those thought to be responsible for the symptoms of mental illness.
However in case of hypothyroidism this needs to be referred to a doctor.

Practitioners of orthodox medicine and psychology are not trained in nutritional medicine and tend to overlook and ignore the nutritional aspects of emotional disorders.

The physical treatment of depression is of prime importance and this is not to say that psychotherapy has no role. Provided it is understood that psychotherapy cannot cure a PHYSICAL AILMENT , it can be used to teach a person how to avoid social stress situations. A psychotherapist should always be aware that a presenting symptom discussed in an interview is not one that indicates a DISEASE. He/she should be able to distinguish between a psychological problem (self-image, lack of assertiveness) from a physical symptoms such as an unexplainable mood swings or depression. This can be tested with the NBI.

Stress hormones interfere with the synthesis of beneficial neurotransmitters such as serotonin, especially in those individuals who are genetically disposed to become depressed.

Antidepressant Activities
There are many other natural ways whereby we can reduce the symptoms of depression. There are studies to show that regular physical exercises reduce depression. The following are also known to reduce depression: walking your dog, bicycling, listening to classical music, Yoga, Transcendental meditation, Relaxation Therapy, Massage, attending church and praying, Qigong, T’ai-chi ch’uan, taking up a hobby and so and on. These are all enjoyable and regular stress management techniques that allows to body to produce serotonin and other neurochemicals in the absence of stress hormones.

If you are presently on drugs, you can withdraw from them very gradually under doctor’s supervision, while you are on the hypoglycemic diet.

Please discuss this article with your health care worker, doctor or nutritional doctor or therapist.

Please read:

The Serotonin Connection” .
“What is Hypoglycemia?”
The Hypoglycemic diet
Hypoglycemia – is it a cure all for mental illness?
Depression a Nutritional Disorder
Depression a Disease of Energy Production

McCormick, D.B. 1989. Two interconnected B vitamins: riboflavin and pyridoxine. Physiol. Revs., 69: 1170-98. See here.

Insel, TR (2006),Beyond Efficacy: The STAR*D Trial, Am J Psychiatry 163:5-7, January 2006
Mitchell, T, (1998) Methylation: A little known but essential process

.Werbach,M.R.(1991), NUTRITIONAL INFLUENCES ON MENTAL ILLNESS, Third Line Pres,Inc.,Tarzana,Cal. Chapter on Depression


Depression and Insulin resistance

Hypoglycemia, Diabetes & Depression

Insomnia and Hypoglycemia and Melatonin

Obesity references

Serotonin and carbohydrates (sugars)

More studies on the relationship between depression and insulin resistance here.

4 Responses

  1. Kim says:

    I have been on LexPro for 8 years on and off for anxiety.. Never stay on it for too long because of the weight gain.. And the care free feeling.mhowever I’ve now hit thyroid issues and I believe menapause… OMG now what??? I’m a areobic instructor I’ve done two Triatalons 2 half marathons and now training for a full. I’m going to try this Amoryn and I’m praying to God it helps. I’m getting the worst hormone symptoms plus the brain zaps and very very dizzy… There has to b an answer to all this …. Blood work tomorrow.. Wish me luck!!

    • Jurriaan Plesman says:

      Hi Kim

      I am using my iPhone as my only tool of communications as I am in hospital at present. 
      I hope I won’t make too many typing mistakes. If words are capitalized please look up the term at our web site or google search the term. 

      Lexpro is mainly used for mood disorders such as depression. You might benefit from reading :

    • Edward says:

      Hi KIM:

      I was on Zoloft for two years 25mg.I’m 51 an elite triathlete.
      When I was traning my heart rate was always spiking from 160BPM
      to 195BPM and go down again really enoying.One day in 2012 I did
      the ING in MIAMI half marathon.I run the whole marathon with a heart rate of 195BPM spiking to 210BPM.Next three days I stared to feel very bad ,like chest pain ,but eventually it went away.I was concern about my heart rate while exercising.I met a friend and told him my story ,he recommented me to see his cardiologist.I went and saw the doctor first thing he told me was to get off the Zoloft.I did taper it for 3 weeks than I stopped taking it.First week my heart rate when down 10BPM,second week another 10BPM by the third week
      it had gone 35BPM less.I started to run and I could not get my heart rate past 165BPM.Boy if I was really really happy.I satrted to max out at 172BPM., but later on I started to experience cramps and spasms in my stomach also some type of anxiety and depression.I do suffer from irritable bowel syndrome ,anxiety and depression.
      My doctor than told me to try SAMe or Amoryn.
      I know that antidepressants give you an increase in heart rate,so if you want to keep your heart rate low stay with herbals while you compete.I felt a lot stonger and faster when I was off Zoloft.
      I will try Amoryn or SAM-e and see what happens.

      Keep tranning that exercise will help you more than the drugs.

  2. Jurriaan Plesman says:

    I have noticed that Amoryn is difficult to obtain in Australia. What is the government protecting us against? Why cannont we get it normally in health food stores? Are they protecting Big Pharma?
    Does anybody know,, where we can buy it?

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